rs870707

Positions:

• chr13-95474574-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182848.4(CLDN10):​c.214+40527C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,198 control chromosomes in the GnomAD database, including 1,181 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 0.12 (1181 hom., cov: 33)
• Consequence: CLDN10 NM_182848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN10	NM_001160100.2	c.157+40584C>A		intron_variant
CLDN10	NM_182848.4	c.214+40527C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN10	ENST00000376873.7	c.214+40527C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17625 AN: 152080 Hom.: 1175 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.116 AC: 17646 AN: 152198 Hom.: 1181 Cov.: 33 AF XY: 0.121 AC XY: 9036 AN XY: 74414

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.140

Alfa AF: 0.113 Hom.: 1443

Bravo AF: 0.104

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs870707; hg19: chr13-96126828;