rs4252582
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001289808.2(CRYAB):c.60C>T(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,608,418 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001289808.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CRYAB | NM_001289808.2 | c.60C>T | p.Pro20Pro | synonymous_variant | Exon 1 of 3 | ENST00000650687.2 | NP_001276737.1 | |
CRYAB | NM_001289807.1 | c.60C>T | p.Pro20Pro | synonymous_variant | Exon 2 of 4 | NP_001276736.1 | ||
CRYAB | NM_001368245.1 | c.60C>T | p.Pro20Pro | synonymous_variant | Exon 2 of 4 | NP_001355174.1 | ||
CRYAB | NM_001885.3 | c.60C>T | p.Pro20Pro | synonymous_variant | Exon 2 of 4 | NP_001876.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00114 AC: 173AN: 152154Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00481 AC: 1142AN: 237432Hom.: 31 AF XY: 0.00645 AC XY: 826AN XY: 128096
GnomAD4 exome AF: 0.00240 AC: 3489AN: 1456146Hom.: 102 Cov.: 31 AF XY: 0.00350 AC XY: 2536AN XY: 723594
GnomAD4 genome AF: 0.00114 AC: 174AN: 152272Hom.: 6 Cov.: 32 AF XY: 0.00154 AC XY: 115AN XY: 74464
ClinVar
Submissions by phenotype
not specified Benign:5
Pro20Pro in exon 1 of CRYAB: This variant is not expected to have clinical signi ficance because it has been identified in 8.0% (14/176) of Gujarati Indian chrom osomes from a broad population by the HapMap Project (dbSNP rs4252582). -
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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. -
Dilated cardiomyopathy 1II Benign:1
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Myofibrillar myopathy 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Cardiomyopathy Benign:1
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not provided Benign:1
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Fatal infantile hypertonic myofibrillar myopathy Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Cataract 16 multiple types Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at