NM_001257.5:c.46-96754C>G

Variant names:

• chr16-82761608-C-G
• rs8046812
• NM_001257.5:c.46-96754C>G

Variant summary

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

The NM_001257.5(CDH13):​c.46-96754C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,074 control chromosomes in the GnomAD database, including 6,857 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 0.29 (6857 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-96754C>G		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.46-96754C>G		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44061 AN: 151956 Hom.: 6852 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.290 AC: 44100 AN: 152074 Hom.: 6857 Cov.: 32 AF XY: 0.288 AC XY: 21432 AN XY: 74328

African (AFR) AF: 0.380 AC: 15745 AN: 41480

American (AMR) AF: 0.249 AC: 3800 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5166

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16697 AN: 67960

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.268 Hom.: 769

Bravo AF: 0.300

Asia WGS AF: 0.374 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.34
PhyloP100		1.4
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: rs8046812; hg19: chr16-82795213;