rs219769

Variant names:

• chr21-36463377-C-A
• rs219769
• NM_001146079.2:c.-81-1601G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-36463377-C-A
• chr21-36463377-C-T

Variant summary

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

The NM_001146079.2(CLDN14):​c.-81-1601G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,180 control chromosomes in the GnomAD database, including 6,157 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 0.27 (6157 hom., cov: 33)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	NM_001146079.2	MANE Select	c.-81-1601G>T		intron	N/A	NP_001139551.1
	CLDN14	NM_001146077.2		c.-81-1601G>T		intron	N/A	NP_001139549.1
	CLDN14	NM_001146078.3		c.-81-1601G>T		intron	N/A	NP_001139550.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	ENST00000399135.6	TSL:1 MANE Select	c.-81-1601G>T		intron	N/A	ENSP00000382087.1
	CLDN14	ENST00000342108.2	TSL:1	c.-81-1601G>T		intron	N/A	ENSP00000339292.2
	CLDN14	ENST00000399136.5	TSL:1	c.-81-1601G>T		intron	N/A	ENSP00000382088.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41086 AN: 152062 Hom.: 6135 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.270 AC: 41156 AN: 152180 Hom.: 6157 Cov.: 33 AF XY: 0.263 AC XY: 19559 AN XY: 74402

African (AFR) AF: 0.384 AC: 15950 AN: 41516

American (AMR) AF: 0.235 AC: 3589 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3468

East Asian (EAS) AF: 0.00752 AC: 39 AN: 5184

South Asian (SAS) AF: 0.149 AC: 719 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2243 AN: 10590

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16995 AN: 67992

Other (OTH) AF: 0.280 AC: 593 AN: 2116

Alfa AF: 0.257 Hom.: 6835

Bravo AF: 0.275

Asia WGS AF: 0.114 AC: 399 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	0.20
DANN	Benign	0.44
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs219769; hg19: chr21-37835675;