chr16-83344491-A-G

Variant names:

• chr16-83344491-A-G
• rs1424168
• NM_001257.5:c.637-371A>G

Variant summary

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

The NM_001220488.2(CDH13):​c.778-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 152,316 control chromosomes in the GnomAD database, including 538 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 0.071 (538 hom., cov: 33)
• Consequence: CDH13 NM_001220488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220488.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.637-371A>G		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.778-371A>G		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.520-371A>G		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.637-371A>G		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.778-371A>G		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.520-371A>G		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0713 AC: 10846 AN: 152198 Hom.: 535 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0713 AC: 10855 AN: 152316 Hom.: 538 Cov.: 33 AF XY: 0.0709 AC XY: 5281 AN XY: 74478

African (AFR) AF: 0.0182 AC: 758 AN: 41570

American (AMR) AF: 0.0589 AC: 902 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

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

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10614

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7373 AN: 68020

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0477 Hom.: 51

Bravo AF: 0.0643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.6
DANN	Benign	0.65
PhyloP100		0.33
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: rs1424168; hg19: chr16-83378096;