rs34627708

chr21-36462886-TC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001146079.2(CLDN14):c.-81-1111del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 150,456 control chromosomes in the GnomAD database, including 17,066 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (17066 hom., cov: 0)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

CLDN14 (HGNC:2035): (claudin 14) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. The encoded protein also binds specifically to the WW domain of Yes-associated protein. Defects in this gene are the cause of an autosomal recessive form of nonsyndromic sensorineural deafness. It is also reported that four synonymous variants in this gene are associated with kidney stones and reduced bone mineral density. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]

CLDN14-AS1 (HGNC:55953): (CLDN14 antisense RNA 1)

LNCTSI (HGNC:56660): (lncRNA TGF-beta/SMAD3 pathway interacting)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN14	NM_001146079.2	c.-81-1111del		intron_variant		ENST00000399135.6
CLDN14-AS1	NR_183529.1	n.468+16880del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN14	ENST00000399135.6	c.-81-1111del		intron_variant		1	NM_001146079.2	P1
CLDN14-AS1	ENST00000428667.1	n.277+16880del		intron_variant, non_coding_transcript_variant		5
LNCTSI	ENST00000429588.1	n.54-17344del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 67855 AN: 150336 Hom.: 17061 Cov.: 0

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.451 AC: 67866 AN: 150456 Hom.: 17066 Cov.: 0 AF XY: 0.450 AC XY: 33028 AN XY: 73372

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.480

Alfa AF: 0.336 Hom.: 901

Bravo AF: 0.441

Asia WGS AF: 0.386 AC: 1338 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34627708; hg19: chr21-37835184;