dbSNP rs779074661: CLDN15:p.Glu189Lys (chr7-101232620-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014343.3(CLDN15):c.565G>A(p.Glu189Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,589,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CLDN15
NM_014343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.638

Publications

0 publications found

Variant links:

Genes affected

CLDN15 (HGNC:2036): (claudin 15) 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. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]

CLDN15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0658997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN15	NM_014343.3	MANE Select	c.565G>A	p.Glu189Lys	missense	Exon 4 of 5	NP_055158.1	P56746
	CLDN15	NM_001185080.2		c.565G>A	p.Glu189Lys	missense	Exon 5 of 6	NP_001172009.1	P56746

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN15	ENST00000308344.10	TSL:1 MANE Select	c.565G>A	p.Glu189Lys	missense	Exon 4 of 5	ENSP00000308870.5	P56746
CLDN15	ENST00000401528.5	TSL:2	c.565G>A	p.Glu189Lys	missense	Exon 5 of 6	ENSP00000385300.1	P56746
CLDN15	ENST00000412417.1	TSL:5	c.496G>A	p.Glu166Lys	missense	Exon 4 of 4	ENSP00000390230.1	C9JHQ4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197164

AF XY:

0.0000185

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000244

AC:

AN:

1436972

Hom.:

Cov.:

AF XY:

0.0000252

AC XY:

AN XY:

713052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33068

American (AMR)

AF:

0.00

AC:

AN:

39890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25524

East Asian (EAS)

AF:

0.00

AC:

AN:

38708

South Asian (SAS)

AF:

0.00

AC:

AN:

83888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

1100176

Other (OTH)

AF:

0.0000169

AC:

AN:

59324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000566

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000841

AC:

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

Benign

0.078

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.096

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.54

M_CAP

Benign

0.040

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.0

PhyloP100

0.64

PrimateAI

Benign

0.39

PROVEAN

Benign

0.48

REVEL

Benign

0.14

Sift

Benign

0.85

Sift4G

Benign

0.92

Polyphen

0.0080

Vest4

0.22

MutPred

0.39

Gain of methylation at E189 (P = 0.0095)

MVP

0.75

MPC

0.36

ClinPred

0.071

GERP RS

1.6

Varity_R

0.064

gMVP

0.32

Mutation Taster

=90/10

polymorphism

(source)

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

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