21-36477203-A-G

Variant names:

• chr21-36477203-A-G
• rs2850110
• NM_001146079.2:c.-82+2292T>C

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+2292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,256 control chromosomes in the GnomAD database, including 57,557 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 0.87 (57557 hom., cov: 33)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146079.2	c.-82+2292T>C		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+2292T>C		intron_variant	Intron 1 of 1	1	NM_001146079.2	ENSP00000382087.1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132094 AN: 152138 Hom.: 57501 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.868 AC: 132207 AN: 152256 Hom.: 57557 Cov.: 33 AF XY: 0.867 AC XY: 64542 AN XY: 74448

African (AFR) AF: 0.903 AC: 37514 AN: 41548

American (AMR) AF: 0.887 AC: 13567 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2900 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3608 AN: 5166

South Asian (SAS) AF: 0.794 AC: 3830 AN: 4824

European-Finnish (FIN) AF: 0.876 AC: 9297 AN: 10610

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58609 AN: 68014

Other (OTH) AF: 0.847 AC: 1792 AN: 2116

Alfa AF: 0.869 Hom.: 7442

Bravo AF: 0.871

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.21
PhyloP100		-0.23
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: rs2850110; hg19: chr21-37849501;