rs12917991

Positions:

• chr16-83231507-C-A
• chr16-83231507-C-G
• chr16-83231507-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001257.5(CDH13):​c.636+14010C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 152,210 control chromosomes in the GnomAD database, including 110 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 0.037 (110 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0373 (5671/152210) while in subpopulation AFR AF= 0.0505 (2098/41536). AF 95% confidence interval is 0.0487. There are 110 homozygotes in gnomad4. There are 2849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 110 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.636+14010C>A		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.636+14010C>A		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5664 AN: 152092 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0373 AC: 5671 AN: 152210 Hom.: 110 Cov.: 32 AF XY: 0.0383 AC XY: 2849 AN XY: 74408

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0358

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0142 Hom.: 2

Bravo AF: 0.0371

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs12917991; hg19: chr16-83265112;