16-83031764-G-C

Position:

• chr16-83031764-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001257.5(CDH13):​c.158-246G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,150 control chromosomes in the GnomAD database, including 1,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1530 hom., cov: 30)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 16-83031764-G-C is Benign according to our data. Variant chr16-83031764-G-C is described in ClinVar as [Benign]. Clinvar id is 1253546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.158-246G>C		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.158-246G>C		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19668 AN: 152032 Hom.: 1531 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.129 AC: 19678 AN: 152150 Hom.: 1530 Cov.: 30 AF XY: 0.130 AC XY: 9686 AN XY: 74386

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0210 Hom.: 9

Bravo AF: 0.138

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs35178368; hg19: chr16-83065369;