rs9984896

Variant names:

• chr21-36563371-A-C
• rs9984896
• ENST00000342108.2:c.-220+13040T>G

Variant summary

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

The ENST00000342108.2(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 ENST00000342108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342108.2. 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_001146077.2		c.-220+13040T>G		intron	N/A	NP_001139549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	ENST00000342108.2	TSL:1	c.-220+13040T>G		intron	N/A	ENSP00000339292.2
	LNCTSI	ENST00000715798.1		n.469-63624A>C		intron	N/A

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

African (AFR) AF: 0.0426 AC: 1768 AN: 41482

American (AMR) AF: 0.0967 AC: 1478 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3472

East Asian (EAS) AF: 0.0692 AC: 358 AN: 5172

South Asian (SAS) AF: 0.128 AC: 615 AN: 4804

European-Finnish (FIN) AF: 0.163 AC: 1720 AN: 10562

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12768 AN: 67974

Other (OTH) AF: 0.125 AC: 265 AN: 2116

Alfa AF: 0.153 Hom.: 3654

Bravo AF: 0.120

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.029
DANN	Benign	0.38
PhyloP100		-2.9
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: rs9984896; hg19: chr21-37935669;