chr16-83521920-A-G

Variant names:

• chr16-83521920-A-G
• rs4074373
• NM_001257.5:c.960+35265A>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.960+35265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,304 control chromosomes in the GnomAD database, including 884 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 0.10 (884 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 8 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=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.960+35265A>G		intron_variant	Intron 7 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.960+35265A>G		intron_variant	Intron 7 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1101+35265A>G		intron_variant	Intron 8 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.843+35265A>G		intron_variant	Intron 6 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*592+35265A>G		intron_variant	Intron 6 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15523 AN: 152186 Hom.: 883 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.102 AC: 15528 AN: 152304 Hom.: 884 Cov.: 33 AF XY: 0.103 AC XY: 7707 AN XY: 74472

African (AFR) AF: 0.0515 AC: 2142 AN: 41578

American (AMR) AF: 0.0921 AC: 1409 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.0508 AC: 263 AN: 5182

South Asian (SAS) AF: 0.166 AC: 800 AN: 4832

European-Finnish (FIN) AF: 0.145 AC: 1537 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8895 AN: 68010

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

Alfa AF: 0.111 Hom.: 1198

Bravo AF: 0.0941

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4074373; hg19: chr16-83555525;