rs9984896

Positions:

• chr21-36563371-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146077.2(CLDN14):​c.-220+13040T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,066 control chromosomes in the GnomAD database, including 1,622 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 0.13 (1622 hom., cov: 31)
• Consequence: CLDN14 NM_001146077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN14	NM_001146077.2	c.-220+13040T>G		intron_variant			NP_001139549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000342108.2	c.-220+13040T>G		intron_variant		1		ENSP00000339292.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19835 AN: 151948 Hom.: 1621 Cov.: 31

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.130 AC: 19836 AN: 152066 Hom.: 1622 Cov.: 31 AF XY: 0.129 AC XY: 9562 AN XY: 74338

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.125

Alfa AF: 0.171 Hom.: 2482

Bravo AF: 0.120

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.029
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9984896; hg19: chr21-37935669;