rs60419768

chr21-36462866-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001146079.2(CLDN14):c.-81-1090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 136,998 control chromosomes in the GnomAD database, including 42 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 0.024 (42 hom., cov: 30)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

CLDN14-AS1 (HGNC:55953): (CLDN14 antisense RNA 1)

LNCTSI (HGNC:56660): (lncRNA TGF-beta/SMAD3 pathway interacting)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.024 (3286/136998) while in subpopulation AFR AF= 0.0398 (1608/40374). AF 95% confidence interval is 0.0382. There are 42 homozygotes in gnomad4. There are 1564 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN14	NM_001146079.2	c.-81-1090G>A		intron_variant		ENST00000399135.6
CLDN14-AS1	NR_183529.1	n.468+16859C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN14	ENST00000399135.6	c.-81-1090G>A		intron_variant		1	NM_001146079.2	P1
CLDN14-AS1	ENST00000428667.1	n.277+16859C>T		intron_variant, non_coding_transcript_variant		5
LNCTSI	ENST00000429588.1	n.54-17365C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3281 AN: 136882 Hom.: 42 Cov.: 30

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.00997

Gnomad MID AF: 0.0136

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0247

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

GnomAD4 genome AF: 0.0240 AC: 3286 AN: 136998 Hom.: 42 Cov.: 30 AF XY: 0.0235 AC XY: 1564 AN XY: 66610

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.0287

Gnomad4 FIN AF: 0.00997

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0249

Alfa AF: 0.0185 Hom.: 5

Bravo AF: 0.0223

Asia WGS AF: 0.0330 AC: 114 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.29
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs60419768; hg19: chr21-37835164;