chr3-150940477-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195794.1(CLRN1):c.472+4C>T variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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
NM_001195794.1 splice_region, intron

Scores

Splicing: ADA: 0.004845

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.452

Variant links:

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]

CLRN1 links:

ENSG00000260234 (HGNC:):

ENSG00000260234 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
CLRN1	NM_174878.3 link	c.433+1105C>T		intron_variant	Intron 2 of 2	ENST00000327047.6	NP_777367.1	P58418-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047.6 link	c.433+1105C>T		intron_variant	Intron 2 of 2	1	NM_174878.3	ENSP00000322280.1		P58418-3
ENSG00000260234	ENST00000569170.5 link	n.160+1105C>T		intron_variant	Intron 1 of 10	1		ENSP00000457784.1		H3BUT2

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4854

AN:

152172

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.0603

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00459

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0492

AC:

6602

AN:

134086

Hom.:

663

AF XY:

0.0452

AC XY:

3302

AN XY:

73020

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.0630

Gnomad ASJ exome

AF:

0.00314

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.00383

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0171

AC:

23576

AN:

1382388

Hom.:

2160

Cov.:

AF XY:

0.0174

AC XY:

11847

AN XY:

682154

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.0595

Gnomad4 ASJ exome

AF:

0.00326

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.0405

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.0342

GnomAD4 genome

AF:

0.0319

AC:

4859

AN:

152290

Hom.:

330

Cov.:

AF XY:

0.0355

AC XY:

2646

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0370

Gnomad4 AMR

AF:

0.0413

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0345

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 20, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

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). -

Usher syndrome type 3A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0048

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over