NM_001257.5:c.961-43626C>T

Variant names:

• chr16-83558828-C-T
• rs4238692
• NM_001257.5:c.961-43626C>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.961-43626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,002 control chromosomes in the GnomAD database, including 7,250 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 0.31 (7250 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.961-43626C>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.961-43626C>T		intron_variant	Intron 7 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1102-43626C>T		intron_variant	Intron 8 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.844-43626C>T		intron_variant	Intron 6 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*593-43626C>T		intron_variant	Intron 6 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46680 AN: 151884 Hom.: 7244 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.307 AC: 46709 AN: 152002 Hom.: 7250 Cov.: 32 AF XY: 0.305 AC XY: 22671 AN XY: 74320

African (AFR) AF: 0.356 AC: 14751 AN: 41426

American (AMR) AF: 0.243 AC: 3720 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1132 AN: 5158

South Asian (SAS) AF: 0.264 AC: 1269 AN: 4806

European-Finnish (FIN) AF: 0.319 AC: 3369 AN: 10568

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20661 AN: 67970

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.224 Hom.: 790

Bravo AF: 0.305

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.60
PhyloP100		-0.31
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: rs4238692; hg19: chr16-83592433;