rs3796242

Positions:

chr3-150972652-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_174878.3(CLRN1):c.57A>T(p.Ala19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,614,088 control chromosomes in the GnomAD database, including 13,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1293 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11749 hom. )

Consequence

CLRN1
NM_174878.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.790

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:

(HGNC:):

links:

CLRN1-AS1 (HGNC:30895): (CLRN1 antisense RNA 1)

CLRN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-150972652-T-A is Benign according to our data. Variant chr3-150972652-T-A is described in ClinVar as [Benign]. Clinvar id is 48147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-150972652-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLRN1	NM_174878.3 linkuse as main transcript	c.57A>T	p.Ala19=	synonymous_variant	1/3	ENST00000327047.6	NP_777367.1
CLRN1-AS1	NR_024066.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047.6 linkuse as main transcript	c.57A>T	p.Ala19=	synonymous_variant	1/3	1	NM_174878.3	ENSP00000322280	P1	P58418-3
	ENST00000469268.1 linkuse as main transcript	n.236-28922T>A		intron_variant, non_coding_transcript_variant		4
CLRN1-AS1	ENST00000476886.5 linkuse as main transcript	n.124-90274T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18707

AN:

152088

Hom.:

1290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.0853

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.0935

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.135

AC:

33883

AN:

251334

Hom.:

2662

AF XY:

0.132

AC XY:

17887

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.0776

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.0955

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.123

AC:

179866

AN:

1461882

Hom.:

11749

Cov.:

AF XY:

0.122

AC XY:

88923

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0861

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.0750

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.0992

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.123

AC:

18722

AN:

152206

Hom.:

1293

Cov.:

AF XY:

0.129

AC XY:

9595

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0904

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.0853

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.0940

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.114

Hom.:

328

Bravo

AF:

0.120

Asia WGS

AF:

0.162

AC:

562

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.117

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 07, 2008	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Usher syndrome type 3A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Usher syndrome type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

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