rs1215

Positions:

• chr17-7260031-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001307.6(CLDN7):​c.*343T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 335,210 control chromosomes in the GnomAD database, including 3,378 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1294 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2084 hom.)
• Consequence: CLDN7 NM_001307.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN7	NM_001307.6	c.*343T>C		3_prime_UTR_variant	4/4	ENST00000360325.11	NP_001298.3
CLDN7	NM_001185022.2	c.*343T>C		3_prime_UTR_variant	5/5		NP_001171951.1
CLDN7	NM_001185023.2	c.*456T>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	c.*343T>C		3_prime_UTR_variant	4/4	1	NM_001307.6	ENSP00000353475.7
ENSG00000262302	ENST00000577138.1	n.223+1790T>C		intron_variant		3		ENSP00000460571.1
CLDN7	ENST00000538261.7	c.*456T>C		3_prime_UTR_variant	3/3	5		ENSP00000445131.2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17600 AN: 152040 Hom.: 1278 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.139 AC: 25469 AN: 183052 Hom.: 2084 Cov.: 4 AF XY: 0.143 AC XY: 13499 AN XY: 94450

Gnomad4 AFR exome AF: 0.0315

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0883

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.116 AC: 17644 AN: 152158 Hom.: 1294 Cov.: 32 AF XY: 0.117 AC XY: 8691 AN XY: 74388

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.140

Alfa AF: 0.148 Hom.: 1388

Bravo AF: 0.121

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1215; hg19: chr17-7163350;