rs61754177
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003183.6(ADAM17):c.2017G>A(p.Val673Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00745 in 1,611,580 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V673V) has been classified as Likely benign.
Frequency
Consequence
NM_003183.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM17 | NM_003183.6 | c.2017G>A | p.Val673Ile | missense_variant | 17/19 | ENST00000310823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM17 | ENST00000310823.8 | c.2017G>A | p.Val673Ile | missense_variant | 17/19 | 1 | NM_003183.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00658 AC: 1001AN: 152192Hom.: 9 Cov.: 33
GnomAD3 exomes AF: 0.00870 AC: 2158AN: 247906Hom.: 14 AF XY: 0.00770 AC XY: 1032AN XY: 133990
GnomAD4 exome AF: 0.00754 AC: 11010AN: 1459270Hom.: 58 Cov.: 30 AF XY: 0.00722 AC XY: 5240AN XY: 725836
GnomAD4 genome ? AF: 0.00657 AC: 1001AN: 152310Hom.: 9 Cov.: 33 AF XY: 0.00615 AC XY: 458AN XY: 74480
ClinVar
Submissions by phenotype
Inflammatory skin and bowel disease, neonatal, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Jul 12, 2022 | This variant has been reported in the literature in association with inflammatory bowel disease (Gettler 2021 PMID:33359885). However, this variant is present in the Genome Aggregation Database (Highest reported MAF 1.2% (196/15286) including multiple homozygotes (https://gnomad.broadinstitute.org/variant/2-9492963-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:539952). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. - |
ADAM17-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at