Variant 16-83670784-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001257.5(CDH13):c.1102-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 1,613,100 control chromosomes in the GnomAD database, including 4,447 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 449 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3998 hom. )

Consequence

CDH13
NM_001257.5 splice_region, intron

Scores

Splicing: ADA: 0.00004345

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.39

Variant links:

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]

CDH13 links:

LOC124900603 (HGNC:):

LOC124900603 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 16-83670784-T-C is Benign according to our data. Variant chr16-83670784-T-C is described in ClinVar as [Benign]. Clinvar id is 257641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5 link	c.1102-6T>C		splice_region_variant, intron_variant		ENST00000567109.6	NP_001248.1	P55290-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6 link	c.1102-6T>C		splice_region_variant, intron_variant		1	NM_001257.5	ENSP00000479395.1		P55290-1

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11027

AN:

152136

Hom.:

448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0944

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.0438

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.00499

Gnomad SAS

AF:

0.0875

Gnomad FIN

AF:

0.0543

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0695

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0662

AC:

16472

AN:

248930

Hom.:

676

AF XY:

0.0685

AC XY:

9244

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.0971

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.00585

Gnomad SAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.0618

Gnomad NFE exome

AF:

0.0703

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.0709

AC:

103614

AN:

1460846

Hom.:

3998

Cov.:

AF XY:

0.0718

AC XY:

52202

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.0944

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.00398

Gnomad4 SAS exome

AF:

0.0914

Gnomad4 FIN exome

AF:

0.0636

Gnomad4 NFE exome

AF:

0.0713

Gnomad4 OTH exome

AF:

0.0733

GnomAD4 genome

AF:

0.0724

AC:

11029

AN:

152254

Hom.:

449

Cov.:

AF XY:

0.0712

AC XY:

5298

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0943

Gnomad4 AMR

AF:

0.0435

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.00501

Gnomad4 SAS

AF:

0.0873

Gnomad4 FIN

AF:

0.0543

Gnomad4 NFE

AF:

0.0695

Gnomad4 OTH

AF:

0.0748

Alfa

AF:

0.0778

Hom.:

478

Bravo

AF:

0.0709

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.0745

EpiControl

AF:

0.0701

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over