rs7184058

Variant names:

• chr16-83236977-G-A
• rs7184058
• NM_001257.5:c.636+19480G>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.636+19480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,904 control chromosomes in the GnomAD database, including 3,636 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 0.22 (3636 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.636+19480G>A		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.636+19480G>A		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32778 AN: 151784 Hom.: 3628 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.216 AC: 32802 AN: 151904 Hom.: 3636 Cov.: 31 AF XY: 0.212 AC XY: 15772 AN XY: 74222

African (AFR) AF: 0.202 AC: 8382 AN: 41420

American (AMR) AF: 0.176 AC: 2685 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3466

East Asian (EAS) AF: 0.0183 AC: 94 AN: 5134

South Asian (SAS) AF: 0.135 AC: 646 AN: 4802

European-Finnish (FIN) AF: 0.264 AC: 2781 AN: 10538

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16596 AN: 67968

Other (OTH) AF: 0.221 AC: 466 AN: 2104

Alfa AF: 0.228 Hom.: 6822

Bravo AF: 0.207

Asia WGS AF: 0.0990 AC: 346 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.15
PhyloP100		-0.12
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: rs7184058; hg19: chr16-83270582;