rs170183

Variant names:

• chr21-36476036-G-A
• rs170183
• NM_001146079.2:c.-82+3459C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-36476036-G-A
• chr21-36476036-G-C
• chr21-36476036-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146079.2(CLDN14):​c.-82+3459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,950 control chromosomes in the GnomAD database, including 14,695 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 0.40 (14695 hom., cov: 31)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146079.2	c.-82+3459C>T		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.-82+3459C>T		intron_variant	Intron 1 of 1	1	NM_001146079.2	ENSP00000382087.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60716 AN: 151832 Hom.: 14689 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.400 AC: 60720 AN: 151950 Hom.: 14695 Cov.: 31 AF XY: 0.403 AC XY: 29932 AN XY: 74236

African (AFR) AF: 0.113 AC: 4693 AN: 41484

American (AMR) AF: 0.459 AC: 7016 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2093 AN: 5150

South Asian (SAS) AF: 0.386 AC: 1860 AN: 4822

European-Finnish (FIN) AF: 0.529 AC: 5562 AN: 10512

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36402 AN: 67922

Other (OTH) AF: 0.406 AC: 856 AN: 2110

Alfa AF: 0.488 Hom.: 85914

Bravo AF: 0.383

Asia WGS AF: 0.350 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs170183; hg19: chr21-37848334;