rs34627708

Variant names:

• chr21-36462886-TC-T
• rs34627708
• NM_001146079.2:c.-81-1111delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001146079.2(CLDN14):​c.-81-1111delG variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 1 publications found

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]

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

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLDN14	NM_001146079.2	c.-81-1111delG		intron_variant	Intron 1 of 1	ENST00000399135.6	NP_001139551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000399135.6	c.-81-1111delG		intron_variant	Intron 1 of 1	1	NM_001146079.2	ENSP00000382087.1

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

African (AFR) AF: 0.220 AC: 8968 AN: 40846

American (AMR) AF: 0.486 AC: 7372 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1829 AN: 3462

East Asian (EAS) AF: 0.444 AC: 2260 AN: 5086

South Asian (SAS) AF: 0.384 AC: 1825 AN: 4758

European-Finnish (FIN) AF: 0.509 AC: 5190 AN: 10200

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38823 AN: 67644

Other (OTH) AF: 0.480 AC: 1007 AN: 2100

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs34627708; hg19: chr21-37835184;