chr16-83231507-C-A

Variant names:

• chr16-83231507-C-A
• rs12917991
• NM_001257.5:c.636+14010C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001257.5(CDH13):​c.636+14010C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 152,210 control chromosomes in the GnomAD database, including 110 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 0.037 (110 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 1 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=-0.93).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0373 (5671/152210) while in subpopulation AFR AF = 0.0505 (2098/41536). AF 95% confidence interval is 0.0487. There are 110 homozygotes in GnomAd4. There are 2849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 110 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.636+14010C>A		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.777+14010C>A		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.519+14010C>A		intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.636+14010C>A		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.777+14010C>A		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.519+14010C>A		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5664 AN: 152092 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0373 AC: 5671 AN: 152210 Hom.: 110 Cov.: 32 AF XY: 0.0383 AC XY: 2849 AN XY: 74408

African (AFR) AF: 0.0505 AC: 2098 AN: 41536

American (AMR) AF: 0.0438 AC: 669 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.0315 AC: 163 AN: 5172

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4824

European-Finnish (FIN) AF: 0.0358 AC: 379 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1895 AN: 68014

Other (OTH) AF: 0.0299 AC: 63 AN: 2108

Alfa AF: 0.0142 Hom.: 2

Bravo AF: 0.0371

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.69
PhyloP100		-0.82
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: rs12917991; hg19: chr16-83265112;