chr16-83453711-G-A

Variant names:

• chr16-83453711-G-A
• rs8054845
• NM_001257.5:c.782-32766G>A

Variant summary

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

The NM_001257.5(CDH13):​c.782-32766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,854 control chromosomes in the GnomAD database, including 18,751 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 0.49 (18751 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.8 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.782-32766G>A		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.923-32766G>A		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.665-32766G>A		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.782-32766G>A		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.923-32766G>A		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.665-32766G>A		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73657 AN: 151736 Hom.: 18747 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.485 AC: 73685 AN: 151854 Hom.: 18751 Cov.: 31 AF XY: 0.486 AC XY: 36034 AN XY: 74200

African (AFR) AF: 0.347 AC: 14352 AN: 41392

American (AMR) AF: 0.504 AC: 7695 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4222 AN: 5142

South Asian (SAS) AF: 0.593 AC: 2846 AN: 4798

European-Finnish (FIN) AF: 0.491 AC: 5163 AN: 10512

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35803 AN: 67948

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.520 Hom.: 90427

Bravo AF: 0.479

Asia WGS AF: 0.653 AC: 2273 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	0.83
DANN	Benign	0.47
PhyloP100		-0.29
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: rs8054845; hg19: chr16-83487316;