rs219771

Variant names:

• chr21-36463203-C-T
• rs219771
• NM_001146079.2:c.-81-1427G>A

Variant summary

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

The NM_001146079.2(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 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• 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)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146079.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	NM_001146079.2	MANE Select	c.-81-1427G>A		intron	N/A	NP_001139551.1
	CLDN14	NM_001146077.2		c.-81-1427G>A		intron	N/A	NP_001139549.1
	CLDN14	NM_001146078.3		c.-81-1427G>A		intron	N/A	NP_001139550.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	ENST00000399135.6	TSL:1 MANE Select	c.-81-1427G>A		intron	N/A	ENSP00000382087.1
	CLDN14	ENST00000342108.2	TSL:1	c.-81-1427G>A		intron	N/A	ENSP00000339292.2
	CLDN14	ENST00000399136.5	TSL:1	c.-81-1427G>A		intron	N/A	ENSP00000382088.1

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

African (AFR) AF: 0.446 AC: 18474 AN: 41458

American (AMR) AF: 0.246 AC: 3764 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.00755 AC: 39 AN: 5164

South Asian (SAS) AF: 0.149 AC: 718 AN: 4812

European-Finnish (FIN) AF: 0.212 AC: 2240 AN: 10572

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 17009 AN: 67970

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.264 Hom.: 7757

Bravo AF: 0.297

Asia WGS AF: 0.119 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.95
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: rs219771; hg19: chr21-37835501;