12-120978597-A-AGGGTTGG
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000545.8(HNF1A):c.-160_-154dupTGGGGGT variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00685 in 664,898 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Consequence
NM_000545.8 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.-160_-154dupTGGGGGT | 5_prime_UTR_variant | Exon 1 of 10 | ENST00000257555.11 | NP_000536.6 | ||
HNF1A | NM_001306179.2 | c.-160_-154dupTGGGGGT | 5_prime_UTR_variant | Exon 1 of 10 | NP_001293108.2 | |||
HNF1A | NM_001406915.1 | c.-160_-154dupTGGGGGT | 5_prime_UTR_variant | Exon 1 of 9 | NP_001393844.1 | |||
HNF1A | XM_024449168.2 | c.-160_-154dupTGGGGGT | 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.-160_-154dupTGGGGGT | 5_prime_UTR_variant | Exon 1 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.00641 AC: 935AN: 145940Hom.: 4 Cov.: 31
GnomAD3 exomes AF: 0.00470 AC: 510AN: 108504Hom.: 2 AF XY: 0.00413 AC XY: 242AN XY: 58580
GnomAD4 exome AF: 0.00697 AC: 3618AN: 518856Hom.: 17 Cov.: 5 AF XY: 0.00649 AC XY: 1808AN XY: 278692
GnomAD4 genome AF: 0.00641 AC: 936AN: 146042Hom.: 4 Cov.: 31 AF XY: 0.00706 AC XY: 502AN XY: 71114
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
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HNF1A: BS2 -
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Diabetes mellitus type 1;C0011860:Type 2 diabetes mellitus;C1838100:Maturity-onset diabetes of the young type 3;C1840646:Hepatic adenomas, familial;C2675866:Type 1 diabetes mellitus 20;CN074294:Nonpapillary renal cell carcinoma Benign:1
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Monogenic diabetes Benign:1
The c.-160_-154dup variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.013, which is greater thanthe MDEP threshold for BA1 (greater than or equal to 0.0001) (BA1). Additionally, this variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). In summary, c.-160_-154dup meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): BA1, BP5. -
Maturity onset diabetes mellitus in young Benign: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 rs538476099 with MODY3. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at