Evidence Repository
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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
BS1 PM2

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
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.
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.
Curation History
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