rs55828480

Variant names:

• chr21-36477219-G-A
• rs55828480
• NM_001146079.2:c.-82+2276C>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.-82+2276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,288 control chromosomes in the GnomAD database, including 688 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 0.086 (688 hom., cov: 33)
• Consequence: CLDN14 NM_001146079.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• 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)

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN14	NM_001146079.2	MANE Select	c.-82+2276C>T		intron	N/A	NP_001139551.1	O95500
	CLDN14	NM_001146077.2		c.-81-15443C>T		intron	N/A	NP_001139549.1	O95500
	CLDN14	NM_001146078.3		c.-81-15443C>T		intron	N/A	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.-82+2276C>T		intron	N/A	ENSP00000382087.1	O95500
	CLDN14	ENST00000342108.2	TSL:1	c.-81-15443C>T		intron	N/A	ENSP00000339292.2	O95500
	CLDN14	ENST00000399136.5	TSL:1	c.-81-15443C>T		intron	N/A	ENSP00000382088.1	O95500

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13066 AN: 152170 Hom.: 687 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0802

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

GnomAD4 genome AF: 0.0858 AC: 13069 AN: 152288 Hom.: 688 Cov.: 33 AF XY: 0.0881 AC XY: 6558 AN XY: 74446

African (AFR) AF: 0.133 AC: 5517 AN: 41570

American (AMR) AF: 0.0777 AC: 1189 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.168 AC: 870 AN: 5178

South Asian (SAS) AF: 0.0850 AC: 410 AN: 4824

European-Finnish (FIN) AF: 0.115 AC: 1214 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0518 AC: 3524 AN: 68024

Other (OTH) AF: 0.0799 AC: 169 AN: 2116

Alfa AF: 0.0665 Hom.: 90

Bravo AF: 0.0840

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.70
PhyloP100		-0.076
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: rs55828480; hg19: chr21-37849517;