chr8-66177022-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000756.4(CRH):c.456G>A(p.Arg152Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,614,034 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000756.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRH | NM_000756.4 | c.456G>A | p.Arg152Arg | synonymous_variant | Exon 2 of 2 | ENST00000276571.5 | NP_000747.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00148 AC: 226AN: 152240Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00314 AC: 788AN: 250622Hom.: 8 AF XY: 0.00402 AC XY: 545AN XY: 135514
GnomAD4 exome AF: 0.00225 AC: 3284AN: 1461676Hom.: 21 Cov.: 31 AF XY: 0.00267 AC XY: 1943AN XY: 727120
GnomAD4 genome AF: 0.00148 AC: 225AN: 152358Hom.: 1 Cov.: 32 AF XY: 0.00138 AC XY: 103AN XY: 74498
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:1
This alteration is classified as likely 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. -
CRH-related disorder Benign:1
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