rs12866697

Variant names:

• chr13-95485833-G-A
• rs12866697
• ENST00000416909.1:n.377-5871C>T

Variant summary

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

The ENST00000416909.1(CLDN10-AS1):​n.377-5871C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,976 control chromosomes in the GnomAD database, including 21,909 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 0.53 (21909 hom., cov: 32)
• Consequence: CLDN10-AS1 ENST00000416909.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 3 publications found

Genes affected

CLDN10-AS1 (HGNC:39907): (CLDN10 antisense RNA 1)

CLDN10 (HGNC:2033): (claudin 10) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

CLDN10 Gene-Disease associations (from GenCC):

• HELIX syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics

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 (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_182848.4	c.214+51786G>A		intron_variant	Intron 1 of 4		NP_878268.1
CLDN10	NM_001160100.2	c.157+51843G>A		intron_variant	Intron 1 of 4		NP_001153572.1
CLDN10-AS1	NR_046533.1	n.377-5871C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10-AS1	ENST00000416909.1	n.377-5871C>T		intron_variant	Intron 3 of 3	1
CLDN10	ENST00000376873.7	c.214+51786G>A		intron_variant	Intron 1 of 4	2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80722 AN: 151858 Hom.: 21881 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.628

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.532 AC: 80792 AN: 151976 Hom.: 21909 Cov.: 32 AF XY: 0.529 AC XY: 39295 AN XY: 74272

African (AFR) AF: 0.631 AC: 26137 AN: 41448

American (AMR) AF: 0.514 AC: 7858 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2842 AN: 5166

South Asian (SAS) AF: 0.497 AC: 2395 AN: 4820

European-Finnish (FIN) AF: 0.440 AC: 4634 AN: 10542

Middle Eastern (MID) AF: 0.628 AC: 182 AN: 290

European-Non Finnish (NFE) AF: 0.488 AC: 33152 AN: 67946

Other (OTH) AF: 0.548 AC: 1157 AN: 2110

Alfa AF: 0.509 Hom.: 50365

Bravo AF: 0.537

Asia WGS AF: 0.577 AC: 2001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.055
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: rs12866697; hg19: chr13-96138087;