chr12-121001197-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000545.8(HNF1A):c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 1,613,844 control chromosomes in the GnomAD database, including 5 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_000545.8 3_prime_UTR
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.*5G>A | 3_prime_UTR_variant | Exon 10 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 | |||
C12orf43 | ENST00000288757 | c.*2956C>T | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_022895.3 | ENSP00000288757.5 |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 326AN: 152182Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.000524 AC: 131AN: 250210Hom.: 0 AF XY: 0.000399 AC XY: 54AN XY: 135452
GnomAD4 exome AF: 0.000201 AC: 294AN: 1461544Hom.: 1 Cov.: 33 AF XY: 0.000172 AC XY: 125AN XY: 727046
GnomAD4 genome AF: 0.00217 AC: 330AN: 152300Hom.: 4 Cov.: 33 AF XY: 0.00222 AC XY: 165AN XY: 74472
ClinVar
Submissions by phenotype
not specified Benign:3
- -
- -
Variant summary: HNF1A c.*5G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00052 in 250210 control chromosomes, predominantly at a frequency of 0.0075 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 300 fold of the estimated maximal expected allele frequency for a pathogenic variant in HNF1A causing Maturity Onset Diabetes Of The Young 3 phenotype (2.5e-05). To our knowledge, no occurrence of c.*5G>A in individuals affected with Maturity Onset Diabetes Of The Young 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 377966). Based on the evidence outlined above, the variant was classified as benign. -
Maturity onset diabetes mellitus in young Uncertain:1Benign:1
Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs112986697 with MODY3. -
The c.*5G>A variant is located in the 3' untranslated region (3’ UTR) of the HNF1A gene. This variant results from a G to A substitution five bases downstream of the last translated codon. This variant was previously reported in the SNPDatabase as rs112986697. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.14% (3/2098) total alleles studied. The highest observed frequency was 0.86% (1/116) Mexican-American alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.28% (37/13006) total alleles studied, having been observed in 0.84% (37/4406) African American alleles. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at