Variant 4-17526979-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001079827.2(CLRN2):c.596A>T(p.His199Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000625 in 1,613,816 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

CLRN2
NM_001079827.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.57

Variant links:

Genes affected

CLRN2 (HGNC:33939): (clarin 2) This gene belongs to the clarin family of genes. The clarins appear to belong to a large superfamily of small integral membrane glycoproteins with four transmembrane domains. The exact function of this gene is unknown. [provided by RefSeq, Oct 2008]

CLRN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02322632).

BP6

Variant 4-17526979-A-T is Benign according to our data. Variant chr4-17526979-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048511.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLRN2	NM_001079827.2 linkuse as main transcript	c.596A>T	p.His199Leu	missense_variant	3/3	ENST00000511148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLRN2	ENST00000511148.2 linkuse as main transcript	c.596A>T	p.His199Leu	missense_variant	3/3	1	NM_001079827.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000786

AC:

196

AN:

249276

Hom.:

AF XY:

0.000784

AC XY:

106

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000646

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000620

AC:

906

AN:

1461624

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

489

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.000497

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000677

AC:

103

AN:

152192

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00312

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000619

Hom.:

Bravo

AF:

0.000672

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000232

AC:

ESP6500EA

AF:

0.000822

AC:

ExAC

AF:

0.000717

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CLRN2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.29

Eigen

Benign

-0.0066

Eigen_PC

Benign

0.024

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.39

Vest4

0.54

MVP

0.65

MPC

0.22

ClinPred

0.16

GERP RS

4.5

Varity_R

0.63

gMVP

0.88

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