rs12073994
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000307340.8(USH2A):c.10851C>T(p.Asn3617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,028 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 8 hom. )
Consequence
USH2A
ENST00000307340.8 synonymous
ENST00000307340.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.222
Genes affected
USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 1-215779931-G-A is Benign according to our data. Variant chr1-215779931-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 48360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.222 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00465 (707/152154) while in subpopulation AFR AF= 0.0162 (672/41482). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.10851C>T | p.Asn3617= | synonymous_variant | 55/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.10851C>T | p.Asn3617= | synonymous_variant | 55/72 | 1 | NM_206933.4 | ENSP00000305941 | P1 | |
USH2A | ENST00000674083.1 | c.10851C>T | p.Asn3617= | synonymous_variant | 55/73 | ENSP00000501296 |
Frequencies
GnomAD3 genomes AF: 0.00464 AC: 706AN: 152036Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00138 AC: 346AN: 251406Hom.: 2 AF XY: 0.000979 AC XY: 133AN XY: 135864
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GnomAD4 exome AF: 0.000646 AC: 945AN: 1461874Hom.: 8 Cov.: 32 AF XY: 0.000583 AC XY: 424AN XY: 727240
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GnomAD4 genome AF: 0.00465 AC: 707AN: 152154Hom.: 4 Cov.: 32 AF XY: 0.00429 AC XY: 319AN XY: 74406
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Asn3617Asn in Exon 55 of USH2A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 1.7% (62/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs12073994). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 19, 2021 | - - |
Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Usher syndrome type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at