dbSNP rs3757458: CLDN15:c.-428C>T (chr7-101238122-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN15	NM_001185080.2 link	c.-428C>T		5_prime_UTR_variant	Exon 1 of 6		NP_001172009.1	P56746

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN15	ENST00000401528.5 link	c.-428C>T		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000385300.1		P56746
CLDN15	ENST00000611078.4 link	c.-541C>T		upstream_gene_variant		5		ENSP00000481925.1		Q96FX9

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

Gnomad4 AFR exome

AF:

0.00960

Gnomad4 AMR exome

AF:

0.0612

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.0617

Gnomad4 SAS exome

AF:

0.0446

Gnomad4 FIN exome

AF:

0.0442

Gnomad4 NFE exome

AF:

0.0461

Gnomad4 OTH exome

AF:

0.0364

GnomAD4 genome

AF:

0.0406

AC:

6188

AN:

152268

Hom.:

168

Cov.:

AF XY:

0.0393

AC XY:

2928

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.0332

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.0831

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0519

Gnomad4 NFE

AF:

0.0540

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0496

Hom.:

202

Bravo

AF:

0.0392

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

DANN

Benign

0.81

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over