chr16-83493987-G-A

Variant names:

• chr16-83493987-G-A
• rs7195409
• NM_001257.5:c.960+7332G>A

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+7332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,030 control chromosomes in the GnomAD database, including 36,074 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 0.68 (36074 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.960+7332G>A		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.1101+7332G>A		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.843+7332G>A		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.960+7332G>A		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.1101+7332G>A		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.843+7332G>A		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103111 AN: 151912 Hom.: 36060 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.679 AC: 103163 AN: 152030 Hom.: 36074 Cov.: 32 AF XY: 0.683 AC XY: 50742 AN XY: 74318

African (AFR) AF: 0.488 AC: 20221 AN: 41438

American (AMR) AF: 0.673 AC: 10269 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2576 AN: 3472

East Asian (EAS) AF: 0.875 AC: 4517 AN: 5162

South Asian (SAS) AF: 0.809 AC: 3904 AN: 4824

European-Finnish (FIN) AF: 0.763 AC: 8056 AN: 10564

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51290 AN: 67990

Other (OTH) AF: 0.658 AC: 1390 AN: 2112

Alfa AF: 0.630 Hom.: 4103

Bravo AF: 0.660

Asia WGS AF: 0.815 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.69
PhyloP100		-1.7
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: rs7195409; hg19: chr16-83527592;