rs404515

Variant names:

• chr21-36563890-G-A
• rs404515
• ENST00000342108.2:c.-220+12521C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-36563890-G-A
• chr21-36563890-G-C

Variant summary

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

The ENST00000342108.2(CLDN14):​c.-220+12521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,242 control chromosomes in the GnomAD database, including 60,655 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 0.89 (60655 hom., cov: 32)
• Consequence: CLDN14 ENST00000342108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 4 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146077.2	c.-220+12521C>T		intron_variant	Intron 1 of 2		NP_001139549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000342108.2	c.-220+12521C>T		intron_variant	Intron 1 of 2	1		ENSP00000339292.2
LNCTSI	ENST00000715798.1	n.469-63105G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135115 AN: 152124 Hom.: 60600 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.888 AC: 135229 AN: 152242 Hom.: 60655 Cov.: 32 AF XY: 0.877 AC XY: 65256 AN XY: 74406

African (AFR) AF: 0.975 AC: 40509 AN: 41562

American (AMR) AF: 0.766 AC: 11712 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.673 AC: 3481 AN: 5172

South Asian (SAS) AF: 0.813 AC: 3920 AN: 4822

European-Finnish (FIN) AF: 0.775 AC: 8196 AN: 10582

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61218 AN: 68022

Other (OTH) AF: 0.893 AC: 1886 AN: 2112

Alfa AF: 0.874 Hom.: 24690

Bravo AF: 0.889

Asia WGS AF: 0.738 AC: 2570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.57
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs404515; hg19: chr21-37936188;