chr13-95552554-G-A

Position:

• chr13-95552554-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182848.4(CLDN10):​c.215-7578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 249,818 control chromosomes in the GnomAD database, including 937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (651 hom., cov: 33)
  • Exomes 𝑓: 0.079 (286 hom.)
• Consequence: CLDN10 NM_182848.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.754

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-95552554-G-A is Benign according to our data. Variant chr13-95552554-G-A is described in ClinVar as [Benign]. Clinvar id is 1222730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN10	NM_182848.4	c.215-7578G>A		intron_variant			NP_878268.1
CLDN10	NM_001160100.2	c.158-7578G>A		intron_variant			NP_001153572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000376873.7	c.215-7578G>A		intron_variant		2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12228 AN: 152084 Hom.: 649 Cov.: 33

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.0961

GnomAD4 exome AF: 0.0792 AC: 7733 AN: 97628 Hom.: 286 AF XY: 0.0795 AC XY: 3749 AN XY: 47164

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0774

Gnomad4 OTH exome AF: 0.0991

GnomAD4 genome AF: 0.0804 AC: 12241 AN: 152190 Hom.: 651 Cov.: 33 AF XY: 0.0831 AC XY: 6181 AN XY: 74404

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0701

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0326 Hom.: 25

Bravo AF: 0.0838

Asia WGS AF: 0.142 AC: 495 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277421; hg19: chr13-96204808;