chr11-34456207-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP6BS2
The NM_001752.4(CAT):c.903+5G>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,607,840 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001752.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAT | NM_001752.4 | c.903+5G>T | splice_donor_5th_base_variant, intron_variant | ENST00000241052.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAT | ENST00000241052.5 | c.903+5G>T | splice_donor_5th_base_variant, intron_variant | 1 | NM_001752.4 | P1 | |||
CAT | ENST00000650153.1 | c.*723+5G>T | splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant | ||||||
CAT | ENST00000528104.2 | n.273+5G>T | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00189 AC: 288AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00288 AC: 716AN: 248270Hom.: 3 AF XY: 0.00366 AC XY: 494AN XY: 134832
GnomAD4 exome AF: 0.00272 AC: 3963AN: 1455570Hom.: 20 Cov.: 29 AF XY: 0.00310 AC XY: 2244AN XY: 724514
GnomAD4 genome AF: 0.00188 AC: 286AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.00196 AC XY: 146AN XY: 74460
ClinVar
Submissions by phenotype
Acatalasia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous c.903+5G>T variant in CAT has been identified in 2 Hungarian relatives from 1 family with hypocatalasaemia (PMID: 11197178), and has been identified in >1% of South Asian chromosomes and 1 homozygote by ExAC (http://gnomad.broadinstitute.org/). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. In summary, the clinical significance of this variant is uncertain. - |
CAT-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at