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]
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_175914.5(HNF4A):c.123C>T (p.Cys41=)

CA9870170

586013 (ClinVar)

Gene: HNF4A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 200610b4-3fb6-4d7b-8343-1ef281f7a9ca
Approved on: 2023-01-12
Published on: 2023-01-12

HGVS expressions

NM_175914.5:c.123C>T
NM_175914.5(HNF4A):c.123C>T (p.Cys41=)
NC_000020.11:g.44406131C>T
CM000682.2:g.44406131C>T
NC_000020.10:g.43034771C>T
CM000682.1:g.43034771C>T
NC_000020.9:g.42468185C>T
NG_009818.1:g.55331C>T
ENST00000316099.10:c.189C>T
ENST00000619550.5:n.163C>T
ENST00000681977.1:n.165C>T
ENST00000682169.1:n.142C>T
ENST00000683148.1:n.165C>T
ENST00000683657.1:n.165C>T
ENST00000684046.1:n.165C>T
ENST00000684136.1:n.165C>T
ENST00000684476.1:n.146C>T
ENST00000316099.9:c.189C>T
ENST00000316099.8:c.189C>T
ENST00000316673.8:c.123C>T
ENST00000372920.1:c.280C>T
ENST00000415691.2:c.189C>T
ENST00000443598.6:c.189C>T
ENST00000457232.5:c.123C>T
ENST00000609262.5:c.114C>T
ENST00000609795.5:c.123C>T
ENST00000619550.4:c.114C>T
NM_000457.4:c.189C>T
NM_001030003.2:c.123C>T
NM_001030004.2:c.123C>T
NM_001258355.1:c.168C>T
NM_001287182.1:c.114C>T
NM_001287183.1:c.114C>T
NM_001287184.1:c.114C>T
NM_175914.4:c.123C>T
NM_178849.2:c.189C>T
NM_178850.2:c.189C>T
NM_001030003.3:c.123C>T
NM_001030004.3:c.123C>T
NM_001258355.2:c.168C>T
NM_001287182.2:c.114C>T
NM_001287184.2:c.114C>T
NM_178849.3:c.189C>T
NM_178850.3:c.189C>T
NM_000457.5:c.189C>T
NM_000457.6:c.189C>T
NM_001287183.2:c.114C>T
More

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 2
PM2 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.123C>T variant in the hepatocyte nuclear factor 4 alpha gene, HNF4A, is a synonymous (silent) variant at codon 41 (p.(Cys41=)) of NM_175914.5. This variant is not predicted by SpliceAI to impact splicing (SpliceAI score of 0, which is less than the MDEP cutoff of 0.2) and is not highly conserved (phyloP100way score of -0.297, which is below the MDEP cutoff of 2.0) (BP4, BP7). The Popmax frequency of the c.123C>T variant in gnomAD v2.1.1 is 0.00002295, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. In summary, c.123C>T meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.0, approved 11/16/22): BP4, BP7.
Met criteria codes
BP7
This synonymous variant is not predicted by SpliceAI to impact splicing (SpliceAI score of 0, which is less than the MDEP cutoff of 0.2) and is not highly conserved (phyloP100way score of -0.297, which is below the MDEP cutoff of 2.0) (BP7).
BP4
The computational splicing predictor SpliceAI gives a score of 0 for donor/acceptor loss, suggesting that the variant has no impact on splicing.
Not Met criteria codes
PM2
The Popmax frequency of the c.123C>T variant in gnomAD v2.1.1 is 0.00002295, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
BS1
The Popmax frequency of the c.123C>T variant in gnomAD v2.1.1 is 0.00002295, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.