rs7204129

Positions:

• chr16-83631072-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.1101+28478C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,074 control chromosomes in the GnomAD database, including 9,396 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 0.35 (9396 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1101+28478C>G		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1101+28478C>G		intron_variant		1	NM_001257.5	P1
CDH13	ENST00000268613.14	c.1242+28478C>G		intron_variant		2
CDH13	ENST00000428848.7	c.984+28478C>G		intron_variant		2
CDH13	ENST00000539548.6	c.*733+28478C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53080 AN: 151956 Hom.: 9392 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.349 AC: 53114 AN: 152074 Hom.: 9396 Cov.: 33 AF XY: 0.353 AC XY: 26257 AN XY: 74334

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.345

Alfa AF: 0.357 Hom.: 1261

Bravo AF: 0.342

Asia WGS AF: 0.432 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs7204129; hg19: chr16-83664677;