16-83586864-C-T

Variant names:

• chr16-83586864-C-T
• rs7499397
• NM_001257.5:c.961-15590C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.961-15590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,980 control chromosomes in the GnomAD database, including 24,946 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 0.56 (24946 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 7 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.961-15590C>T		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.961-15590C>T		intron_variant	Intron 7 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1102-15590C>T		intron_variant	Intron 8 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.844-15590C>T		intron_variant	Intron 6 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*593-15590C>T		intron_variant	Intron 6 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85116 AN: 151862 Hom.: 24924 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.560 AC: 85175 AN: 151980 Hom.: 24946 Cov.: 32 AF XY: 0.561 AC XY: 41684 AN XY: 74284

African (AFR) AF: 0.384 AC: 15928 AN: 41430

American (AMR) AF: 0.684 AC: 10456 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3199 AN: 5164

South Asian (SAS) AF: 0.585 AC: 2819 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6283 AN: 10540

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42913 AN: 67958

Other (OTH) AF: 0.552 AC: 1168 AN: 2116

Alfa AF: 0.605 Hom.: 84866

Bravo AF: 0.559

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.27
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: rs7499397; hg19: chr16-83620469;