chr16-83327170-T-C

Variant names:

• chr16-83327170-T-C
• rs9940464
• NM_001257.5:c.637-17692T>C

Variant summary

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

The NM_001257.5(CDH13):​c.637-17692T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,030 control chromosomes in the GnomAD database, including 12,170 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 0.40 (12170 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 9 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

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.637-17692T>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.778-17692T>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.520-17692T>C		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.637-17692T>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.778-17692T>C		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.520-17692T>C		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60031 AN: 151912 Hom.: 12157 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.395 AC: 60075 AN: 152030 Hom.: 12170 Cov.: 33 AF XY: 0.397 AC XY: 29473 AN XY: 74300

African (AFR) AF: 0.303 AC: 12564 AN: 41484

American (AMR) AF: 0.457 AC: 6984 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2515 AN: 5160

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4386 AN: 10552

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29386 AN: 67958

Other (OTH) AF: 0.404 AC: 855 AN: 2114

Alfa AF: 0.394 Hom.: 6986

Bravo AF: 0.395

Asia WGS AF: 0.424 AC: 1474 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.53
PhyloP100		1.7
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: rs9940464; hg19: chr16-83360775;