rs141625803
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001101426.4(CRPPA):āc.1220T>Cā(p.Leu407Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,601,278 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L407L) has been classified as Likely benign.
Frequency
Consequence
NM_001101426.4 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 |
---|---|---|---|---|---|---|---|
CRPPA | NM_001101426.4 | c.1220T>C | p.Leu407Ser | missense_variant | 9/10 | ENST00000407010.7 | |
CRPPA-AS1 | NR_038947.1 | n.118+5494A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRPPA | ENST00000407010.7 | c.1220T>C | p.Leu407Ser | missense_variant | 9/10 | 5 | NM_001101426.4 | P1 | |
CRPPA-AS1 | ENST00000438573.5 | n.116+5494A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00196 AC: 299AN: 152234Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00234 AC: 569AN: 242910Hom.: 10 AF XY: 0.00224 AC XY: 295AN XY: 131498
GnomAD4 exome AF: 0.00105 AC: 1519AN: 1448926Hom.: 29 Cov.: 27 AF XY: 0.00108 AC XY: 777AN XY: 720808
GnomAD4 genome ? AF: 0.00196 AC: 299AN: 152352Hom.: 3 Cov.: 33 AF XY: 0.00212 AC XY: 158AN XY: 74506
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 22, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 15, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2018 | 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. - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Congenital Muscular Dystrophy, alpha-dystroglycan related 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at