Variant 17-7260912-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001307.6(CLDN7):c.297G>A(p.Thr99Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000752 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 0 hom. )

Consequence

CLDN7
NM_001307.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

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:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024683446).

BP6

Variant 17-7260912-C-T is Benign according to our data. Variant chr17-7260912-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709182.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN7	NM_001307.6 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	2/4	ENST00000360325.11	NP_001298.3	O95471-1A0A384ME58
CLDN7	NM_001185022.2 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	3/5		NP_001171951.1	O95471-1A0A384ME58
CLDN7	NM_001185023.2 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	2/3		NP_001171952.1	O95471F5H496

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	2/4	1	NM_001307.6	ENSP00000353475.7		O95471-1
ENSG00000262302	ENST00000577138.1 linkuse as main transcript	n.223+909G>A		intron_variant		3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000497

AC:

125

AN:

251340

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000781

AC:

1142

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

553

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000990

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000473

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000595

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

4.2

DANN

Benign

0.92

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.27

M_CAP

Benign

0.023

MetaRNN

Benign

0.025

Sift4G

Benign

0.29

Vest4

0.10

MVP

0.90

GERP RS

-9.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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