rs3796242

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_174878.3(CLRN1):c.57A>T(p.Ala19Ala) 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

Publications

20 publications found

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:

ENSG00000243273 (HGNC:):

ENSG00000243273 links:

SIAH2-AS1 (HGNC:40526): (SIAH2 antisense RNA 1)

SIAH2-AS1 links:

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

CLRN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 48147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CLRN1	NM_174878.3 link	c.57A>T	p.Ala19Ala	synonymous_variant	Exon 1 of 3	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.57A>T	p.Ala19Ala	synonymous_variant	Exon 1 of 3	1	NM_174878.3	ENSP00000322280.1		P58418-3

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

GnomAD2 exomes

AF:

0.135

AC:

33883

AN:

251334

AF XY:

0.132

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 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

African (AFR)

AF:

0.0861

AC:

2884

AN:

33480

American (AMR)

AF:

0.159

AC:

7123

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0750

AC:

1959

AN:

26136

East Asian (EAS)

AF:

0.212

AC:

8435

AN:

39700

South Asian (SAS)

AF:

0.0992

AC:

8558

AN:

86258

European-Finnish (FIN)

AF:

0.185

AC:

9899

AN:

53416

Middle Eastern (MID)

AF:

0.110

AC:

634

AN:

5768

European-Non Finnish (NFE)

AF:

0.119

AC:

132695

AN:

1112004

Other (OTH)

AF:

0.127

AC:

7679

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

10486

20972

31457

41943

52429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4906

9812

14718

19624

24530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.123

AC:

18722

AN:

152206

Hom.:

1293

Cov.:

AF XY:

0.129

AC XY:

9595

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0904

AC:

3754

AN:

41530

American (AMR)

AF:

0.154

AC:

2355

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

296

AN:

3470

East Asian (EAS)

AF:

0.243

AC:

1261

AN:

5184

South Asian (SAS)

AF:

0.0940

AC:

453

AN:

4820

European-Finnish (FIN)

AF:

0.198

AC:

2094

AN:

10590

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8075

AN:

68014

Other (OTH)

AF:

0.130

AC:

274

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

825

1650

2475

3300

4125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mar 05, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jan 07, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Usher syndrome type 3A

Benign:2

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Usher syndrome type 3

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

(source)

DANN

Benign

0.77

PhyloP100

-0.79

PromoterAI

0.044

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over