rs4562

Variant names:

• chr17-7260420-A-G
• rs4562
• NM_001307.6:c.590T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7260420-A-G
• chr17-7260420-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37838 hom., cov: 32)
  • Exomes 𝑓: 0.63 (293416 hom.)
• Consequence: CLDN7 NM_001307.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 58 publications found

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]

ENSG00000262302 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLDN7	NM_001307.6	c.590T>C	p.Val197Ala	missense_variant	Exon 4 of 4	ENST00000360325.11	NP_001298.3
CLDN7	NM_001185022.2	c.590T>C	p.Val197Ala	missense_variant	Exon 5 of 5		NP_001171951.1
CLDN7	NM_001185023.2	c.*67T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001171952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11	c.590T>C	p.Val197Ala	missense_variant	Exon 4 of 4	1	NM_001307.6	ENSP00000353475.7
ENSG00000262302	ENST00000577138.1	n.223+1401T>C		intron_variant	Intron 1 of 3	3		ENSP00000460571.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106130 AN: 151954 Hom.: 37769 Cov.: 32

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

GnomAD2 exomes AF: 0.653 AC: 163393 AN: 250316 AF XY: 0.653

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 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.: 53 AF XY: 0.634 AC XY: 460496 AN XY: 726886

African (AFR) AF: 0.861 AC: 28809 AN: 33470

American (AMR) AF: 0.582 AC: 25995 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16784 AN: 26068

East Asian (EAS) AF: 0.642 AC: 25485 AN: 39690

South Asian (SAS) AF: 0.671 AC: 57870 AN: 86206

European-Finnish (FIN) AF: 0.664 AC: 35394 AN: 53340

Middle Eastern (MID) AF: 0.754 AC: 4349 AN: 5766

European-Non Finnish (NFE) AF: 0.620 AC: 689370 AN: 1111620

Other (OTH) AF: 0.646 AC: 39005 AN: 60364

GnomAD4 genome AF: 0.699 AC: 106266 AN: 152072 Hom.: 37838 Cov.: 32 AF XY: 0.700 AC XY: 52064 AN XY: 74348

African (AFR) AF: 0.847 AC: 35137 AN: 41508

American (AMR) AF: 0.649 AC: 9906 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3381 AN: 5144

South Asian (SAS) AF: 0.674 AC: 3248 AN: 4818

European-Finnish (FIN) AF: 0.679 AC: 7193 AN: 10586

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.632 AC: 42953 AN: 67970

Other (OTH) AF: 0.701 AC: 1478 AN: 2108

Alfa AF: 0.656 Hom.: 88682

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	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.047	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.055	.;T
MetaRNN	Benign	8.2e-7	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N;N
PhyloP100		1.1
PrimateAI	Benign	0.36	T
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	T
GERP RS		4.9
Varity_R		0.030
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4562; hg19: chr17-7163739; COSMIC: COSV63038719; COSMIC: COSV63038719;