21-36557014-T-C

Variant names:

• chr21-36557014-T-C
• rs424282
• ENST00000342108.2:c.-220+19397A>G

Variant summary

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

The NM_001146077.2(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 NM_001146077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146077.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	NM_001146077.2		c.-220+19397A>G		intron	N/A	NP_001139549.1	O95500

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	ENST00000342108.2	TSL:1	c.-220+19397A>G		intron	N/A	ENSP00000339292.2	O95500
	LNCTSI	ENST00000715798.1		n.469-69981T>C		intron	N/A

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

African (AFR) AF: 0.801 AC: 33216 AN: 41494

American (AMR) AF: 0.748 AC: 11439 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3206 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3474 AN: 5174

South Asian (SAS) AF: 0.813 AC: 3922 AN: 4826

European-Finnish (FIN) AF: 0.774 AC: 8195 AN: 10590

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61168 AN: 68028

Other (OTH) AF: 0.854 AC: 1806 AN: 2114

Alfa AF: 0.853 Hom.: 7677

Bravo AF: 0.832

Asia WGS AF: 0.726 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.44
PhyloP100		-0.74
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: rs424282; hg19: chr21-37929312;