Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.*4188G>C

CA10644605

339794 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 912add43-9404-4257-a2a6-c545861ad7ef
Approved on: 2021-05-26
Published on: 2022-07-08

HGVS expressions

NM_001754.4:c.*4188G>C
NM_001754.4(RUNX1):c.*4188G>C
NC_000021.9:g.34787947C>G
CM000683.2:g.34787947C>G
NC_000021.8:g.36160244C>G
CM000683.1:g.36160244C>G
NC_000021.7:g.35082114C>G
NG_011402.2:g.1201765G>C
ENST00000675419.1:c.*4188G>C
ENST00000300305.7:c.*4188G>C
ENST00000344691.8:c.*4188G>C
ENST00000437180.5:c.*4188G>C
NM_001001890.2:c.*4188G>C
NM_001001890.3:c.*4188G>C
NM_001754.5:c.*4188G>C
NM_001754.5(RUNX1):c.*4188G>C
More

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 25
PVS1 BA1 BS2 BS4 BS3 BP7 BP5 BP3 BP2 BP4 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM2 PM1 PM4 PM3 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
This 3' UTR c.*4188G>C variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP = -0.665764 in GRCh38). The variant is present in gnomAD at an allele frequency between 0.015% and 0.15% in a general continental population (European, non-Finnish, subpopulation: 0.03528% in v3) with >5 variant alleles and a minimum of 2000 total alleles (BS1) and has not been described in the literature. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1.
Met criteria codes
BS1
Variant is present in >=5 alleles in the European (non-Finnish) population (has required minimum of 2000 alleles) with an MAF of 0.03528% (v3.1.1), which is within the BS1 thresholds (0.015%-0.15%). - gnomAD v2.1.1: ALL: 0.009554% (3/31402) - NFE: 0.01297% (2/15424) - OTH: 0.09208% (1/1086) - gnomAD v3.1.1: ALL: 0.02168% (33/152196) - NFE: 0.03528% (24/38024) - AMR: 0.02616% (4/15290) - ASJ: 0.05760% (2/3472) - OTH: 0.09579% (2/2088)
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Variant is present in >=5 alleles in the European (non-Finnish) population (has required minimum of 2000 alleles) with an MAF of 0.03528% (v3.1.1), which is within the BS1 thresholds (0.015%-0.15%). - gnomAD v2.1.1: ALL: 0.009554% (3/31402) - NFE: 0.01297% (2/15424) - OTH: 0.09208% (1/1086) - gnomAD v3.1.1: ALL: 0.02168% (33/152196) - NFE: 0.03528% (24/38024) - AMR: 0.02616% (4/15290) - ASJ: 0.05760% (2/3472) - OTH: 0.09579% (2/2088)
BS2
Not applicable
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
3'UTR variant that is located at a non-conserved nucleotide (PhyloP = -0.665764 in GRCh38), and the variant is the reference nucleotide in one primate and/or 3 mammals.
BP5
Not applicable
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No donor/acceptor gains or losses predicted (SpliceAI Δ score <= 0.2), but does not apply for UTR variants.
BP1
Not applicable
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No literature found in HGMD, Google+Google Scholar searches, or COSMIC.
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No donor/acceptor gains or losses predicted with SpliceAI Δ score >= 0.38.
PP2
Not applicable
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Variant is present in >=5 alleles in the European (non-Finnish) population (has required minimum of 2000 alleles) with an MAF of 0.03528% (v3.1.1), which is within the BS1 thresholds (0.015%-0.15%). - gnomAD v2.1.1: ALL: 0.009554% (3/31402) - NFE: 0.01297% (2/15424) - OTH: 0.09208% (1/1086) - gnomAD v3.1.1: ALL: 0.02168% (33/152196) - NFE: 0.03528% (24/38024) - AMR: 0.02616% (4/15290) - ASJ: 0.05760% (2/3472) - OTH: 0.09579% (2/2088)
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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