rs74141403
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_206933.4(USH2A):c.11048-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,718 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 19 hom. )
Consequence
USH2A
NM_206933.4 splice_polypyrimidine_tract, intron
NM_206933.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.288
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 1-215759858-G-A is Benign according to our data. Variant chr1-215759858-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215759858-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1047/152162) while in subpopulation AFR AF= 0.0238 (986/41510). AF 95% confidence interval is 0.0225. There are 12 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.11048-15C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.11048-15C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_206933.4 | P1 | |||
USH2A | ENST00000674083.1 | c.11048-15C>T | splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00685 AC: 1042AN: 152046Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00184 AC: 462AN: 250778Hom.: 8 AF XY: 0.00155 AC XY: 210AN XY: 135556
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GnomAD4 exome AF: 0.000770 AC: 1126AN: 1461556Hom.: 19 Cov.: 31 AF XY: 0.000725 AC XY: 527AN XY: 727104
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GnomAD4 genome ? AF: 0.00688 AC: 1047AN: 152162Hom.: 12 Cov.: 32 AF XY: 0.00678 AC XY: 504AN XY: 74382
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | 11048-15C>T in Exon 57 of USH2A: This variant is not expected to have clinical s ignificance because it has been identified in 2.6% (96/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs74141403). - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 18, 2021 | - - |
Retinitis pigmentosa 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Usher syndrome type 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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Name
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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