NM_001257.5:c.960+47786A>G

Variant names:

• chr16-83534441-A-G
• rs11861722
• NM_001257.5:c.960+47786A>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+47786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,114 control chromosomes in the GnomAD database, including 2,194 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 0.15 (2194 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.960+47786A>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+47786A>G		intron_variant	Intron 7 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1101+47786A>G		intron_variant	Intron 8 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.843+47786A>G		intron_variant	Intron 6 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*592+47786A>G		intron_variant	Intron 6 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23008 AN: 151994 Hom.: 2191 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.151 AC: 23026 AN: 152114 Hom.: 2194 Cov.: 33 AF XY: 0.146 AC XY: 10820 AN XY: 74342

African (AFR) AF: 0.276 AC: 11430 AN: 41432

American (AMR) AF: 0.0982 AC: 1502 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3468

East Asian (EAS) AF: 0.0599 AC: 310 AN: 5176

South Asian (SAS) AF: 0.191 AC: 922 AN: 4824

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10604

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7636 AN: 67994

Other (OTH) AF: 0.144 AC: 303 AN: 2110

Alfa AF: 0.127 Hom.: 2383

Bravo AF: 0.162

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.80
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11861722; hg19: chr16-83568046;