rs547523762

Variant names:

• chr21-36460761-AT-A
• rs547523762
• NM_001146079.2:c.*214delA

Your query was ambiguous. Multiple possible variants found:

• chr21-36460761-AT-A
• chr21-36460761-AT-ATT
• chr21-36460761-AT-ATTT
• chr21-36460761-AT-ATTTT
• chr21-36460761-AT-ATTTTTTTTTTTTT
• chr21-36460761-AT-ATTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001146079.2(CLDN14):​c.*214delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 526,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: CLDN14 NM_001146079.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 0 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)

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146079.2. 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_001146079.2	MANE Select	c.*214delA		3_prime_UTR	Exon 2 of 2	NP_001139551.1	O95500
	CLDN14	NM_001146077.2		c.*214delA		3_prime_UTR	Exon 3 of 3	NP_001139549.1	O95500
	CLDN14	NM_001146078.3		c.*214delA		3_prime_UTR	Exon 3 of 3	NP_001139550.1	O95500

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	ENST00000399135.6	TSL:1 MANE Select	c.*214delA		3_prime_UTR	Exon 2 of 2	ENSP00000382087.1	O95500
	CLDN14	ENST00000342108.2	TSL:1	c.*214delA		3_prime_UTR	Exon 3 of 3	ENSP00000339292.2	O95500
	CLDN14	ENST00000399136.5	TSL:1	c.*214delA		3_prime_UTR	Exon 3 of 3	ENSP00000382088.1	O95500

Frequencies

GnomAD3 genomes AF: 0.000305 AC: 46 AN: 150856 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00215 AC: 809 AN: 375544 Hom.: 0 Cov.: 4 AF XY: 0.00220 AC XY: 429 AN XY: 195188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00305 AC: 33 AN: 10824

American (AMR) AF: 0.00229 AC: 35 AN: 15316

Ashkenazi Jewish (ASJ) AF: 0.00163 AC: 19 AN: 11638

East Asian (EAS) AF: 0.00169 AC: 45 AN: 26630

South Asian (SAS) AF: 0.00246 AC: 82 AN: 33348

European-Finnish (FIN) AF: 0.00262 AC: 65 AN: 24784

Middle Eastern (MID) AF: 0.00180 AC: 3 AN: 1666

European-Non Finnish (NFE) AF: 0.00210 AC: 482 AN: 229250

Other (OTH) AF: 0.00204 AC: 45 AN: 22088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000305 AC: 46 AN: 150972 Hom.: 0 Cov.: 32 AF XY: 0.000393 AC XY: 29 AN XY: 73780

African (AFR) AF: 0.00102 AC: 42 AN: 41168

American (AMR) AF: 0.0000661 AC: 1 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67646

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs547523762; hg19: chr21-37833059; COSMIC: COSV59772962; COSMIC: COSV59772962;