rs424282

Positions:

• chr21-36557014-T-C
• chr21-36557014-T-A
• chr21-36557014-T-G

Variant summary

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

The ENST00000342108.2(CLDN14):​c.-220+19397A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,190 control chromosomes in the GnomAD database, including 53,898 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 0.84 (53898 hom., cov: 32)
• Consequence: CLDN14 ENST00000342108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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=-1.0).
• 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/exons	MANE	UniProt
CLDN14	NM_001146077.2	c.-220+19397A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN14	ENST00000342108.2	c.-220+19397A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127459 AN: 152072 Hom.: 53875 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.838 AC: 127535 AN: 152190 Hom.: 53898 Cov.: 32 AF XY: 0.829 AC XY: 61669 AN XY: 74410

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.854

Alfa AF: 0.853 Hom.: 7408

Bravo AF: 0.832

Asia WGS AF: 0.726 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs424282; hg19: chr21-37929312;