rs646094
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_206933.4(USH2A):c.3812-8T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,608,604 control chromosomes in the GnomAD database, including 41,222 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_206933.4 splice_region, splice_polypyrimidine_tract, 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 | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.3812-8T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000307340.8 | |||
USH2A-AS1 | XR_922596.4 | n.691+2667A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.3812-8T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_206933.4 | P1 | |||
USH2A | ENST00000366942.3 | c.3812-8T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
USH2A-AS1 | ENST00000420867.1 | n.362+2667A>C | intron_variant, non_coding_transcript_variant | 3 | |||||
USH2A | ENST00000674083.1 | c.3812-8T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.205 AC: 31090AN: 151976Hom.: 3257 Cov.: 32
GnomAD3 exomes AF: 0.213 AC: 52476AN: 246022Hom.: 5684 AF XY: 0.217 AC XY: 28907AN XY: 133382
GnomAD4 exome AF: 0.226 AC: 329796AN: 1456510Hom.: 37962 Cov.: 32 AF XY: 0.228 AC XY: 165060AN XY: 724752
GnomAD4 genome ? AF: 0.204 AC: 31103AN: 152094Hom.: 3260 Cov.: 32 AF XY: 0.201 AC XY: 14917AN XY: 74334
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 19, 2008 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 10, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2013 | 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. - |
Usher syndrome type 2A Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
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, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Retinitis pigmentosa Benign:1
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at