16-83494417-A-G

Variant names:

• chr16-83494417-A-G
• rs1387370
• NM_001257.5:c.960+7762A>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+7762A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,006 control chromosomes in the GnomAD database, including 20,662 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 0.51 (20662 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.960+7762A>G		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1101+7762A>G		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.843+7762A>G		intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.960+7762A>G		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1101+7762A>G		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.843+7762A>G		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78184 AN: 151888 Hom.: 20645 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.515 AC: 78234 AN: 152006 Hom.: 20662 Cov.: 33 AF XY: 0.514 AC XY: 38185 AN XY: 74300

African (AFR) AF: 0.412 AC: 17060 AN: 41432

American (AMR) AF: 0.531 AC: 8115 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3468

East Asian (EAS) AF: 0.835 AC: 4321 AN: 5172

South Asian (SAS) AF: 0.558 AC: 2694 AN: 4824

European-Finnish (FIN) AF: 0.497 AC: 5253 AN: 10564

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37202 AN: 67960

Other (OTH) AF: 0.493 AC: 1039 AN: 2106

Alfa AF: 0.538 Hom.: 16411

Bravo AF: 0.512

Asia WGS AF: 0.679 AC: 2358 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		-0.38
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: rs1387370; hg19: chr16-83528022; COSMIC: COSV107274868;