chr1-216084723-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_206933.4(USH2A):c.5142T>C(p.Asn1714=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000635 in 1,613,344 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00087 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 8 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.14
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=-0.78).
BP6
?
Variant 1-216084723-A-G is Benign according to our data. Variant chr1-216084723-A-G is described in ClinVar as [Benign]. Clinvar id is 48529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-216084723-A-G is described in Lovd as [Benign]. Variant chr1-216084723-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-4.14 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000874 (133/152238) while in subpopulation EAS AF= 0.0199 (103/5166). AF 95% confidence interval is 0.0168. There are 1 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.5142T>C | p.Asn1714= | synonymous_variant | 25/72 | ENST00000307340.8 | |
USH2A-AS2 | NR_125992.1 | n.266-1999A>G | intron_variant, non_coding_transcript_variant | ||||
USH2A-AS2 | NR_125993.1 | n.137-1999A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.5142T>C | p.Asn1714= | synonymous_variant | 25/72 | 1 | NM_206933.4 | P1 | |
USH2A-AS2 | ENST00000446411.5 | n.266-1999A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000881 AC: 134AN: 152120Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00164 AC: 411AN: 250536Hom.: 3 AF XY: 0.00150 AC XY: 203AN XY: 135378
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GnomAD4 exome AF: 0.000610 AC: 891AN: 1461106Hom.: 8 Cov.: 30 AF XY: 0.000625 AC XY: 454AN XY: 726866
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 26, 2015 | p.Asn1714Asn in exon 25 of USH2A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence and has been reported in 1.9% (162/8634) of Ea st Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs143546878). - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 25, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 13, 2018 | This variant is associated with the following publications: (PMID: 19737284, 22135276) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Usher syndrome type 2A Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 07, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Retinitis pigmentosa 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Retinal dystrophy Benign:1
Benign, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at