rs8054295

Variant names:

• chr16-82676367-T-C
• rs8054295
• NM_001257.5:c.45+49230T>C

Variant summary

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

The NM_001257.5(CDH13):​c.45+49230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,050 control chromosomes in the GnomAD database, including 2,146 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 0.13 (2146 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+49230T>C		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.45+49230T>C		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20100 AN: 151932 Hom.: 2132 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 20139 AN: 152050 Hom.: 2146 Cov.: 31 AF XY: 0.133 AC XY: 9853 AN XY: 74326

African (AFR) AF: 0.287 AC: 11879 AN: 41434

American (AMR) AF: 0.0912 AC: 1394 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 260 AN: 3468

East Asian (EAS) AF: 0.0615 AC: 318 AN: 5170

South Asian (SAS) AF: 0.123 AC: 594 AN: 4810

European-Finnish (FIN) AF: 0.0894 AC: 946 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0652 AC: 4436 AN: 67988

Other (OTH) AF: 0.120 AC: 253 AN: 2110

Alfa AF: 0.124 Hom.: 342

Bravo AF: 0.138

Asia WGS AF: 0.110 AC: 381 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	0.44
DANN	Benign	0.53
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8054295; hg19: chr16-82709972;