Variant chr16-3015980-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021195.5(CLDN6):c.42A>G(p.Thr14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,614,086 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 112 hom., cov: 34)

Exomes 𝑓: 0.0025 ( 82 hom. )

Consequence

CLDN6
NM_021195.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.46

Variant links:

Genes affected

CLDN6 (HGNC:2048): (claudin 6) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. This gene encodes a component of tight junction strands, which is a member of the claudin family. The protein is an integral membrane protein and is one of the entry cofactors for hepatitis C virus. The gene methylation may be involved in esophageal tumorigenesis. This gene is adjacent to another family member CLDN9 on chromosome 16.[provided by RefSeq, Aug 2010]

CLDN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-3015980-T-C is Benign according to our data. Variant chr16-3015980-T-C is described in ClinVar as [Benign]. Clinvar id is 768741.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-8.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN6	NM_021195.5 linkuse as main transcript	c.42A>G	p.Thr14=	synonymous_variant	2/2	ENST00000328796.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CLDN6	ENST00000328796.5 linkuse as main transcript	c.42A>G	p.Thr14=	synonymous_variant	2/2	1	NM_021195.5	P1
CLDN6	ENST00000396925.1 linkuse as main transcript	c.42A>G	p.Thr14=	synonymous_variant	3/3	5		P1
CLDN6	ENST00000572154.1 linkuse as main transcript	c.42A>G	p.Thr14=	synonymous_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3008

AN:

152206

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0663

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00570

AC:

1420

AN:

249260

Hom.:

AF XY:

0.00427

AC XY:

576

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.0683

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000940

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00253

AC:

3702

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1650

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.00563

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000576

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.0199

AC:

3030

AN:

152324

Hom.:

112

Cov.:

AF XY:

0.0193

AC XY:

1437

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0667

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.066

DANN

Benign

0.57

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