rs219771

Positions:

• chr21-36463203-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399135.6(CLDN14):​c.-81-1427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,060 control chromosomes in the GnomAD database, including 7,312 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 0.29 (7312 hom., cov: 32)
• Consequence: CLDN14 ENST00000399135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN14	NM_001146079.2	c.-81-1427G>A		intron_variant		ENST00000399135.6	NP_001139551.1
CLDN14-AS1	NR_183529.1	n.469-17028C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000399135.6	c.-81-1427G>A		intron_variant		1	NM_001146079.2	ENSP00000382087	P1
CLDN14-AS1	ENST00000428667.1	n.277+17196C>T		intron_variant, non_coding_transcript_variant		5
LNCTSI	ENST00000429588.1	n.54-17028C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43843 AN: 151942 Hom.: 7284 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43917 AN: 152060 Hom.: 7312 Cov.: 32 AF XY: 0.281 AC XY: 20879 AN XY: 74344

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.298

Alfa AF: 0.273 Hom.: 1230

Bravo AF: 0.297

Asia WGS AF: 0.119 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.64

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: rs219771; hg19: chr21-37835501;