12-120978621-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000545.8(HNF1A):c.-148C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 764,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000545.8 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.-148C>A | 5_prime_UTR_variant | Exon 1 of 10 | ENST00000257555.11 | NP_000536.6 | ||
HNF1A | NM_001306179.2 | c.-148C>A | 5_prime_UTR_variant | Exon 1 of 10 | NP_001293108.2 | |||
HNF1A | NM_001406915.1 | c.-148C>A | 5_prime_UTR_variant | Exon 1 of 9 | NP_001393844.1 | |||
HNF1A | XM_024449168.2 | c.-148C>A | 5_prime_UTR_variant | Exon 1 of 9 | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555 | c.-148C>A | 5_prime_UTR_variant | Exon 1 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 151094Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000710 AC: 1AN: 140786Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 77808
GnomAD4 exome AF: 0.0000130 AC: 8AN: 613228Hom.: 0 Cov.: 8 AF XY: 0.0000152 AC XY: 5AN XY: 328658
GnomAD4 genome AF: 0.00000662 AC: 1AN: 151094Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73704
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: HNF1A c.-148C>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 1.2e-05 in 760170 control chromosomes, predominantly at a frequency of 2e-05 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is comparable to the estimated maximum expected for a pathogenic variant in HNF1A causing Maturity Onset Diabetes Of The Young 3 phenotype (2.5e-05), suggesting that the variant might be benign. To our knowledge, no occurrence of c.-148C>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. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at