Variant rs4562 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001307.6(CLDN7):c.590T>C(p.Val197Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,613,244 control chromosomes in the GnomAD database, including 331,254 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.70 ( 37838 hom., cov: 32)

Exomes 𝑓: 0.63 ( 293416 hom. )

Consequence

CLDN7
NM_001307.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

CLDN7 (HGNC:2049): (claudin 7) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

CLDN7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.1873384E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLDN7	NM_001307.6 linkuse as main transcript	c.590T>C	p.Val197Ala	missense_variant	4/4	ENST00000360325.11	NP_001298.3
CLDN7	NM_001185022.2 linkuse as main transcript	c.590T>C	p.Val197Ala	missense_variant	5/5		NP_001171951.1
CLDN7	NM_001185023.2 linkuse as main transcript	c.*67T>C		3_prime_UTR_variant	3/3		NP_001171952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 linkuse as main transcript	c.590T>C	p.Val197Ala	missense_variant	4/4	1	NM_001307.6	ENSP00000353475	P1	O95471-1
CLDN7	ENST00000397317.8 linkuse as main transcript	c.590T>C	p.Val197Ala	missense_variant	5/5	1		ENSP00000396638	P1	O95471-1
CLDN7	ENST00000538261.7 linkuse as main transcript	c.*67T>C		3_prime_UTR_variant	3/3	5		ENSP00000445131
CLDN7	ENST00000574070.5 linkuse as main transcript			downstream_gene_variant		1		ENSP00000460550

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106130

AN:

151954

Hom.:

37769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.633

Gnomad EAS

AF:

0.658

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.679

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.697

GnomAD3 exomes

AF:

0.653

AC:

163393

AN:

250316

Hom.:

54155

AF XY:

0.653

AC XY:

88424

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.655

Gnomad SAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.640

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.632

AC:

923061

AN:

1461172

Hom.:

293416

Cov.:

AF XY:

0.634

AC XY:

460496

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.644

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.671

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.699

AC:

106266

AN:

152072

Hom.:

37838

Cov.:

AF XY:

0.700

AC XY:

52064

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.633

Gnomad4 EAS

AF:

0.657

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.679

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.701

Alfa

AF:

0.653

Hom.:

32757

Bravo

AF:

0.701

ESP6500AA

AF:

0.842

AC:

3710

ESP6500EA

AF:

0.622

AC:

5352

ExAC

AF:

0.658

AC:

79897

Asia WGS

AF:

0.698

AC:

2429

AN:

3478

EpiCase

AF:

0.653

EpiControl

AF:

0.657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.055

.;T

MetaRNN

Benign

8.2e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.18

Sift

Benign

1.0

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.017

MPC

0.48

ClinPred

0.00091

GERP RS

4.9

Varity_R

0.030

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over