16-83605730-G-A

Variant names:

• chr16-83605730-G-A
• rs6563943
• NM_001257.5:c.1101+3136G>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.1101+3136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,080 control chromosomes in the GnomAD database, including 20,952 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 0.49 (20952 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.1101+3136G>A		intron_variant	Intron 8 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.1101+3136G>A		intron_variant	Intron 8 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1242+3136G>A		intron_variant	Intron 9 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.984+3136G>A		intron_variant	Intron 7 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*733+3136G>A		intron_variant	Intron 7 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74159 AN: 151962 Hom.: 20893 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.488 AC: 74277 AN: 152080 Hom.: 20952 Cov.: 32 AF XY: 0.485 AC XY: 36021 AN XY: 74324

African (AFR) AF: 0.790 AC: 32779 AN: 41506

American (AMR) AF: 0.431 AC: 6584 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1706 AN: 5158

South Asian (SAS) AF: 0.394 AC: 1899 AN: 4816

European-Finnish (FIN) AF: 0.341 AC: 3606 AN: 10566

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24752 AN: 67966

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.400 Hom.: 45166

Bravo AF: 0.512

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.73
PhyloP100		-0.94
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: rs6563943; hg19: chr16-83639335;