NM_182848.4:c.214+40527C>A

Variant names:

• chr13-95474574-C-A
• rs870707
• NM_182848.4:c.214+40527C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CLDN10 Gene-Disease associations (from GenCC):

• HELIX syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182848.4. 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
	CLDN10	NM_182848.4		c.214+40527C>A		intron	N/A	NP_878268.1	P78369-2
	CLDN10	NM_001160100.2		c.157+40584C>A		intron	N/A	NP_001153572.1	P78369-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN10	ENST00000376873.7	TSL:2	c.214+40527C>A		intron	N/A	ENSP00000366069.2	P78369-2

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

African (AFR) AF: 0.114 AC: 4751 AN: 41540

American (AMR) AF: 0.0772 AC: 1180 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.0726 AC: 375 AN: 5168

South Asian (SAS) AF: 0.247 AC: 1193 AN: 4824

European-Finnish (FIN) AF: 0.174 AC: 1840 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7246 AN: 67994

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.112 Hom.: 1773

Bravo AF: 0.104

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.76
PhyloP100		1.9
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: rs870707; hg19: chr13-96126828;