17-7260415-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001307.6(CLDN7):c.595C>T(p.Arg199Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,462 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CLDN7
NM_001307.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Publications

4 publications found

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:

ELP5 (HGNC:30617): (elongator acetyltransferase complex subunit 5) Predicted to contribute to tRNA binding activity. Predicted to be involved in positive regulation of cell migration and tRNA modification. Located in cytosol and nucleoplasm. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ELP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06544611).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001307.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN7	NM_001307.6	MANE Select	c.595C>T	p.Arg199Cys	missense	Exon 4 of 4	NP_001298.3
CLDN7	NM_001185022.2		c.595C>T	p.Arg199Cys	missense	Exon 5 of 5	NP_001171951.1	A0A384ME58
CLDN7	NM_001185023.2		c.*72C>T		3_prime_UTR	Exon 3 of 3	NP_001171952.1	F5H496

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN7	ENST00000360325.11	TSL:1 MANE Select	c.595C>T	p.Arg199Cys	missense	Exon 4 of 4	ENSP00000353475.7	O95471-1
CLDN7	ENST00000397317.8	TSL:1	c.595C>T	p.Arg199Cys	missense	Exon 5 of 5	ENSP00000396638.3	O95471-1
ENSG00000262302	ENST00000577138.1	TSL:3	n.223+1406C>T		intron	N/A	ENSP00000460571.1	I3L3M4

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000252

AC:

AN:

250158

AF XY:

0.000274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000181

AC:

265

AN:

1461170

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.000112

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00246

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000209

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000125

AC:

139

AN:

1111652

Other (OTH)

AF:

0.000149

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000250

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Benign

0.023

Eigen_PC

Benign

0.0046

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.065

MetaSVM

Uncertain

0.023

MutationAssessor

Uncertain

2.4

PhyloP100

2.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.42

Sift

Benign

0.033

Sift4G

Benign

0.073

Polyphen

0.97

Vest4

0.41

MVP

0.90

MPC

0.82

ClinPred

0.041

GERP RS

3.9

Varity_R

0.14

gMVP

0.57

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over