rs398591

Variant names:

• chr21-36548471-G-A
• rs398591
• ENST00000342108.2:c.-220+27940C>T

Variant summary

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

The ENST00000342108.2(CLDN14):​c.-220+27940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,130 control chromosomes in the GnomAD database, including 53,176 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 0.83 (53176 hom., cov: 32)
• Consequence: CLDN14 ENST00000342108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146077.2	c.-220+27940C>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+27940C>T		intron_variant	Intron 1 of 2	1		ENSP00000339292.2
LNCTSI	ENST00000715798.1	n.469-78524G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126522 AN: 152012 Hom.: 53159 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.832 AC: 126592 AN: 152130 Hom.: 53176 Cov.: 32 AF XY: 0.823 AC XY: 61207 AN XY: 74364

African (AFR) AF: 0.783 AC: 32459 AN: 41476

American (AMR) AF: 0.744 AC: 11370 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3206 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3418 AN: 5166

South Asian (SAS) AF: 0.815 AC: 3924 AN: 4812

European-Finnish (FIN) AF: 0.773 AC: 8192 AN: 10592

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61126 AN: 68002

Other (OTH) AF: 0.846 AC: 1787 AN: 2112

Alfa AF: 0.840 Hom.: 8785

Bravo AF: 0.825

Asia WGS AF: 0.720 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.44
PhyloP100		-0.34
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: rs398591; hg19: chr21-37920769;