Genetic Variant CLDN15:c.-428C>T (chr7-101238122-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001185080.2(CLDN15):c.-428C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 186,400 control chromosomes in the GnomAD database, including 215 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 0.041 ( 168 hom., cov: 33)

Exomes 𝑓: 0.046 ( 47 hom. )

Consequence

CLDN15
NM_001185080.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185080.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN15	NM_001185080.2		c.-428C>T		5_prime_UTR	Exon 1 of 6	NP_001172009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN15	ENST00000401528.5	TSL:2	c.-428C>T		5_prime_UTR	Exon 1 of 6	ENSP00000385300.1
	CLDN15	ENST00000611078.4	TSL:5	c.-541C>T		upstream_gene	N/A	ENSP00000481925.1

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6178

AN:

152150

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.0827

Gnomad SAS

AF:

0.0464

Gnomad FIN

AF:

0.0519

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0540

Gnomad OTH

AF:

0.0340

GnomAD4 exome

AF:

0.0462

AC:

1577

AN:

34132

Hom.:

Cov.:

AF XY:

0.0471

AC XY:

830

AN XY:

17604

show subpopulations

African (AFR)

AF:

0.00960

AC:

AN:

1666

American (AMR)

AF:

0.0612

AC:

219

AN:

3580

Ashkenazi Jewish (ASJ)

AF:

0.0238

AC:

AN:

588

East Asian (EAS)

AF:

0.0617

AC:

190

AN:

3080

South Asian (SAS)

AF:

0.0446

AC:

181

AN:

4062

European-Finnish (FIN)

AF:

0.0442

AC:

AN:

904

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0461

AC:

861

AN:

18674

Other (OTH)

AF:

0.0364

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

148

222

296

370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.0406

AC:

6188

AN:

152268

Hom.:

168

Cov.:

AF XY:

0.0393

AC XY:

2928

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0139

AC:

576

AN:

41554

American (AMR)

AF:

0.0332

AC:

507

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3470

East Asian (EAS)

AF:

0.0831

AC:

430

AN:

5176

South Asian (SAS)

AF:

0.0471

AC:

227

AN:

4820

European-Finnish (FIN)

AF:

0.0519

AC:

551

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0540

AC:

3674

AN:

68016

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

312

624

935

1247

1559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0486

Hom.:

600

Bravo

AF:

0.0392

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.81

PhyloP100

-1.0

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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