rs201469044
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001367994.1(ITGA7):c.-494A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,611,136 control chromosomes in the GnomAD database, including 1 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_001367994.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 151904Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000204 AC: 49AN: 240224Hom.: 0 AF XY: 0.000161 AC XY: 21AN XY: 130832
GnomAD4 exome AF: 0.000110 AC: 161AN: 1459114Hom.: 1 Cov.: 33 AF XY: 0.000114 AC XY: 83AN XY: 725634
GnomAD4 genome AF: 0.000276 AC: 42AN: 152022Hom.: 0 Cov.: 31 AF XY: 0.000417 AC XY: 31AN XY: 74306
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 06, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 02, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 267 of the ITGA7 protein (p.Ile267Val). This variant is present in population databases (rs201469044, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. ClinVar contains an entry for this variant (Variation ID: 538001). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGA7 protein function with a negative predictive value of 80%. 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. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 15, 2024 | BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at