rs200761715
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_000232.5(SGCB):c.799C>T(p.Arg267Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,084 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R267L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000232.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCB | NM_000232.5 | c.799C>T | p.Arg267Cys | missense_variant | 6/6 | ENST00000381431.10 | |
SGCB | XM_047416074.1 | c.589C>T | p.Arg197Cys | missense_variant | 5/5 | ||
SGCB | XM_047416075.1 | c.502C>T | p.Arg168Cys | missense_variant | 5/5 | ||
SGCB | XM_047416076.1 | c.502C>T | p.Arg168Cys | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.799C>T | p.Arg267Cys | missense_variant | 6/6 | 1 | NM_000232.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000565 AC: 86AN: 152158Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00203 AC: 511AN: 251442Hom.: 11 AF XY: 0.00269 AC XY: 365AN XY: 135888
GnomAD4 exome AF: 0.00107 AC: 1564AN: 1461808Hom.: 28 Cov.: 31 AF XY: 0.00150 AC XY: 1092AN XY: 727210
GnomAD4 genome ? AF: 0.000552 AC: 84AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 23, 2016 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2E Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 13, 2020 | - - |
Limb-girdle muscular dystrophy, recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Qualitative or quantitative defects of beta-sarcoglycan Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Jul 06, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at