20-44355726-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_175914.5(HNF4A):c.-79C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,308,684 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_175914.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152258Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000429 AC: 496AN: 1156308Hom.: 6 Cov.: 16 AF XY: 0.000560 AC XY: 330AN XY: 589248
GnomAD4 genome AF: 0.000210 AC: 32AN: 152376Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74522
ClinVar
Submissions by phenotype
not provided Uncertain:2
This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with HNF4A-related conditions, however it has also been observed in unaffected controls (PMID: 12242469, 21062274). ClinVar contains an entry for this variant (Variation ID: 1442643). Studies have shown that this variant does not significantly alter or has an unclear effect on HNF4A gene expression (PMID: 12242469). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant occurs in a non-coding region of the HNF4A gene. It does not change the encoded amino acid sequence of the HNF4A protein. -
Observed in two unrelated individuals in published literature with maturity onset diabetes of the young (MODY); however, the variant did not segregate completely with the condition in the family of one proband and familial segregation information was not provided for the other proband (PMID: 12242469, 21062274); In-silico analysis and one published study are inconclusive as to whether the variant alters gene function (PMID: 12242469). In the absence of additional RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 12242469, 23014256, 21062274) -
Type 2 diabetes mellitus;C1852093:Maturity-onset diabetes of the young type 1;C4014962:Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at