rs11365554

Variant names:

• chr21-36477645-TC-T
• rs11365554
• NM_001146079.2:c.-82+1849delG

Your query was ambiguous. Multiple possible variants found:

• chr21-36477645-TC-T
• chr21-36477645-TC-TCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001146079.2(CLDN14):​c.-82+1849delG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (14217 hom., cov: 0)
  • Exomes 𝑓: 0.23 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146079.2	c.-82+1849delG		intron_variant	Intron 1 of 1	ENST00000399135.6	NP_001139551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000399135.6	c.-82+1849delG		intron_variant	Intron 1 of 1	1	NM_001146079.2	ENSP00000382087.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59707 AN: 151728 Hom.: 14187 Cov.: 0

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.371

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.231 AC: 6 AN: 26 Hom.: 1 AF XY: 0.182 AC XY: 4 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.208 AC: 5 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.394 AC: 59787 AN: 151844 Hom.: 14217 Cov.: 0 AF XY: 0.389 AC XY: 28878 AN XY: 74204

African (AFR) AF: 0.679 AC: 28099 AN: 41400

American (AMR) AF: 0.333 AC: 5061 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3466

East Asian (EAS) AF: 0.290 AC: 1502 AN: 5180

South Asian (SAS) AF: 0.369 AC: 1768 AN: 4788

European-Finnish (FIN) AF: 0.279 AC: 2939 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18133 AN: 67928

Other (OTH) AF: 0.372 AC: 787 AN: 2116

Alfa AF: 0.152 Hom.: 254

Bravo AF: 0.409

Asia WGS AF: 0.376 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39
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: rs11365554; hg19: chr21-37849943;