rs16846663
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000328863.8(CLRN1):c.472+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,534,678 control chromosomes in the GnomAD database, including 2,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 330 hom., cov: 32)
Exomes 𝑓: 0.017 ( 2160 hom. )
Consequence
CLRN1
ENST00000328863.8 splice_donor_region, intron
ENST00000328863.8 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.004845
2
Clinical Significance
Conservation
PhyloP100: -0.452
Genes affected
CLRN1 (HGNC:12605): (clarin 1) This gene encodes a protein that contains a cytosolic N-terminus, multiple helical transmembrane domains, and an endoplasmic reticulum membrane retention signal, TKGH, in the C-terminus. The encoded protein may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIIa. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 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=-0.83).
BP6
?
Variant 3-150940477-G-A is Benign according to our data. Variant chr3-150940477-G-A is described in ClinVar as [Benign]. Clinvar id is 226524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-150940477-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLRN1 | NM_174878.3 | c.433+1105C>T | intron_variant | ENST00000327047.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLRN1 | ENST00000327047.6 | c.433+1105C>T | intron_variant | 1 | NM_174878.3 | P1 | |||
ENST00000469268.1 | n.235+49607G>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLRN1-AS1 | ENST00000476886.5 | n.123+87871G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0319 AC: 4854AN: 152172Hom.: 330 Cov.: 32
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GnomAD3 exomes AF: 0.0492 AC: 6602AN: 134086Hom.: 663 AF XY: 0.0452 AC XY: 3302AN XY: 73020
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GnomAD4 exome AF: 0.0171 AC: 23576AN: 1382388Hom.: 2160 Cov.: 30 AF XY: 0.0174 AC XY: 11847AN XY: 682154
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GnomAD4 genome ? AF: 0.0319 AC: 4859AN: 152290Hom.: 330 Cov.: 32 AF XY: 0.0355 AC XY: 2646AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2015 | c.472+4C>T in intron 3 of CLRN1: This variant is not expected to have clinical s ignificance because it has been identified at high frequency in multiple populat ions, including in 3.7% (275/7400) of South Asian chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs16846663). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 20, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 15, 2018 | 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 3A Benign:1
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 15, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at