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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_175914.5(HNF4A):c.670+7C>T

CA9870336

447519 (ClinVar)

Gene: HNF4A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 953aae40-b629-49d5-9080-737d65e01305
Approved on: 2025-01-29
Published on: 2025-01-29

HGVS expressions

NM_175914.5:c.670+7C>T
NM_175914.5(HNF4A):c.670+7C>T
NC_000020.11:g.44418519C>T
CM000682.2:g.44418519C>T
NC_000020.10:g.43047159C>T
CM000682.1:g.43047159C>T
NC_000020.9:g.42480573C>T
NG_009818.1:g.67719C>T
ENST00000316673.9:c.670+7C>T
ENST00000316099.10:c.736+7C>T
ENST00000619550.5:c.710+7C>T
ENST00000683148.1:n.712+7C>T
ENST00000683657.1:n.1860+7C>T
ENST00000316099.9:c.736+7C>T
ENST00000316099.8:c.736+7C>T
ENST00000316673.8:c.670+7C>T
ENST00000372920.1:c.*503+7C>T
ENST00000415691.2:c.736+7C>T
ENST00000443598.6:c.736+7C>T
ENST00000457232.5:c.670+7C>T
ENST00000609795.5:c.670+7C>T
ENST00000619550.4:c.661+7C>T
NM_000457.4:c.736+7C>T
NM_001030003.2:c.670+7C>T
NM_001030004.2:c.670+7C>T
NM_001258355.1:c.715+7C>T
NM_001287182.1:c.661+7C>T
NM_001287183.1:c.661+7C>T
NM_001287184.1:c.661+7C>T
NM_175914.4:c.670+7C>T
NM_178849.2:c.736+7C>T
NM_178850.2:c.736+7C>T
NM_001030003.3:c.670+7C>T
NM_001030004.3:c.670+7C>T
NM_001258355.2:c.715+7C>T
NM_001287182.2:c.661+7C>T
NM_001287184.2:c.661+7C>T
NM_178849.3:c.736+7C>T
NM_178850.3:c.736+7C>T
NM_000457.5:c.736+7C>T
NM_000457.6:c.736+7C>T
NM_001287183.2:c.661+7C>T
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Uncertain Significance

Met criteria codes 2
BP4 PP4
Not Met criteria codes 2
PM2 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF4A Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.670+7C>T variant in the HNF4 homeobox A gene, HNF4A, is a single nucleotide variant within intron 6 of NM_175914.5. The computational splicing predictor SpliceAI gives a score of 0.00 for donor loss, suggesting that the variant has no impact on splicing (BP4). This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.00002141 which is lower than the MDEP threshold for BS1 (0.000033) and greater than the MDEP threshold for PM2 (0.000003). This variant was identified in an individual with a clinical history highly specific for HNF4A-MODY (MODY probability calculator result >50% and negative genetic testing for HNF1A) (PP4; internal lab contributor).In summary, c.670+7C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BP4, PP4.
Met criteria codes
BP4
The computational splicing predictor SpliceAI gives a score of 0.00 for donor loss, suggesting that the variant has no impact on splicing (BP4).
PP4
This variant was identified in an individual with a clinical history highly specific for HNF4A-monogenic diabetes (MODY probability calculator result >50% and negative genetic testing for HNF1A) (PP4_Moderate; internal lab contributors).
Not Met criteria codes
PM2
The Grpmax filtering allele frequency of the c.670+7C>T variant in gnomAD v2.1.1 is 0.000021, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
BS1
The Grpmax filtering allele frequency of the c.670+7C>T variant in gnomAD v2.1.1 is 0.000021, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
Curation History
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