rs2075961
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000308.4(CTSA):c.948+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,613,730 control chromosomes in the GnomAD database, including 338,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000308.4 splice_region, intron
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTSA | NM_000308.4 | c.948+7G>A | splice_region_variant, intron_variant | ENST00000646241.3 | NP_000299.3 | |||
CTSA | NM_001127695.3 | c.948+7G>A | splice_region_variant, intron_variant | NP_001121167.1 | ||||
CTSA | NM_001167594.3 | c.897+7G>A | splice_region_variant, intron_variant | NP_001161066.2 | ||||
CTSA | NR_133656.2 | n.1000+7G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTSA | ENST00000646241.3 | c.948+7G>A | splice_region_variant, intron_variant | NM_000308.4 | ENSP00000493613.2 |
Frequencies
GnomAD3 genomes AF: 0.656 AC: 99603AN: 151776Hom.: 32769 Cov.: 31
GnomAD3 exomes AF: 0.664 AC: 167046AN: 251434Hom.: 56127 AF XY: 0.658 AC XY: 89469AN XY: 135900
GnomAD4 exome AF: 0.646 AC: 944114AN: 1461836Hom.: 306144 Cov.: 62 AF XY: 0.645 AC XY: 469373AN XY: 727228
GnomAD4 genome AF: 0.656 AC: 99696AN: 151894Hom.: 32804 Cov.: 31 AF XY: 0.661 AC XY: 49014AN XY: 74204
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 19, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 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. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Combined deficiency of sialidase AND beta galactosidase Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 66% of total chromosomes in ExAC - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at