chr16-83417357-A-G

Variant names:

• chr16-83417357-A-G
• rs17214677
• NM_001257.5:c.782-69120A>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.782-69120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,142 control chromosomes in the GnomAD database, including 1,342 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 (1342 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.782-69120A>G		intron_variant	Intron 6 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.782-69120A>G		intron_variant	Intron 6 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18962 AN: 152024 Hom.: 1337 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.125 AC: 18988 AN: 152142 Hom.: 1342 Cov.: 32 AF XY: 0.125 AC XY: 9287 AN XY: 74360

African (AFR) AF: 0.192 AC: 7980 AN: 41500

American (AMR) AF: 0.0731 AC: 1117 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 326 AN: 3468

East Asian (EAS) AF: 0.122 AC: 628 AN: 5168

South Asian (SAS) AF: 0.0955 AC: 459 AN: 4808

European-Finnish (FIN) AF: 0.144 AC: 1517 AN: 10568

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0976 AC: 6639 AN: 68020

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.106 Hom.: 1330

Bravo AF: 0.123

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		-0.20
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: rs17214677; hg19: chr16-83450962;