chr16-83678830-A-G

Variant names:

• chr16-83678830-A-G
• rs3784943
• NM_001257.5:c.1538+369A>G

Variant summary

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

The NM_001257.5(CDH13):​c.1538+369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,148 control chromosomes in the GnomAD database, including 3,975 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 0.23 (3975 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 12 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]

ENSG00000261103 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.338 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.1538+369A>G		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1679+369A>G		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1421+369A>G		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.1538+369A>G		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1679+369A>G		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1421+369A>G		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34482 AN: 152030 Hom.: 3973 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.227 AC: 34502 AN: 152148 Hom.: 3975 Cov.: 32 AF XY: 0.227 AC XY: 16862 AN XY: 74386

African (AFR) AF: 0.246 AC: 10195 AN: 41500

American (AMR) AF: 0.200 AC: 3058 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1811 AN: 5160

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10586

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14611 AN: 67990

Other (OTH) AF: 0.213 AC: 450 AN: 2116

Alfa AF: 0.220 Hom.: 6414

Bravo AF: 0.226

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.31
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3784943; hg19: chr16-83712435; COSMIC: COSV107274887;