chr16-83588362-A-C

Variant names:

• chr16-83588362-A-C
• rs7200573
• NM_001257.5:c.961-14092A>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.961-14092A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,158 control chromosomes in the GnomAD database, including 36,930 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 0.69 (36930 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 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.961-14092A>C		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.1102-14092A>C		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.844-14092A>C		intron	N/A	NP_001207418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.961-14092A>C		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.1102-14092A>C		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.844-14092A>C		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104861 AN: 152040 Hom.: 36902 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.690 AC: 104940 AN: 152158 Hom.: 36930 Cov.: 33 AF XY: 0.697 AC XY: 51845 AN XY: 74408

African (AFR) AF: 0.550 AC: 22823 AN: 41474

American (AMR) AF: 0.783 AC: 11974 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2623 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4470 AN: 5166

South Asian (SAS) AF: 0.774 AC: 3736 AN: 4824

European-Finnish (FIN) AF: 0.758 AC: 8039 AN: 10600

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48858 AN: 68010

Other (OTH) AF: 0.708 AC: 1498 AN: 2116

Alfa AF: 0.713 Hom.: 65045

Bravo AF: 0.685

Asia WGS AF: 0.819 AC: 2845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.059
DANN	Benign	0.44
PhyloP100		-1.5
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: rs7200573; hg19: chr16-83621967;