Variant 18-66509032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021153.4(CDH19):c.1791C>T(p.Val597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,611,996 control chromosomes in the GnomAD database, including 1,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 192 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1141 hom. )

Consequence

CDH19
NM_021153.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.769

Variant links:

Genes affected

CDH19 (HGNC:1758): (cadherin 19) This gene is one of three related type II cadherin genes situated in a cluster on chromosome 18. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein containing five extracellular cadherin repeats. Loss of cadherins may be associated with cancer formation. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Aug 2012]

CDH19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-66509032-G-A is Benign according to our data. Variant chr18-66509032-G-A is described in ClinVar as [Benign]. Clinvar id is 3059447.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.769 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH19	NM_021153.4 linkuse as main transcript	c.1791C>T	p.Val597=	synonymous_variant	11/12	ENST00000262150.7	NP_066976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH19	ENST00000262150.7 linkuse as main transcript	c.1791C>T	p.Val597=	synonymous_variant	11/12	1	NM_021153.4	ENSP00000262150	P1	Q9H159-1
CDH19	ENST00000579658.5 linkuse as main transcript	c.*137C>T		3_prime_UTR_variant, NMD_transcript_variant	11/12	1		ENSP00000463085
CDH19	ENST00000540086.5 linkuse as main transcript	c.1459-3730C>T		intron_variant		2		ENSP00000439593		Q9H159-2

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

4988

AN:

151840

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0697

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0754

Gnomad FIN

AF:

0.00794

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0371

AC:

9295

AN:

250678

Hom.:

465

AF XY:

0.0339

AC XY:

4586

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0626

Gnomad AMR exome

AF:

0.0920

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.0604

Gnomad FIN exome

AF:

0.00750

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.0272

GnomAD4 exome

AF:

0.0148

AC:

21642

AN:

1460038

Hom.:

1141

Cov.:

AF XY:

0.0154

AC XY:

11218

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.0702

Gnomad4 AMR exome

AF:

0.0873

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.0604

Gnomad4 FIN exome

AF:

0.00940

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0330

AC:

5008

AN:

151958

Hom.:

192

Cov.:

AF XY:

0.0339

AC XY:

2518

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.0428

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0752

Gnomad4 FIN

AF:

0.00794

Gnomad4 NFE

AF:

0.00260

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0377

Asia WGS

AF:

0.101

AC:

349

AN:

3476

EpiCase

AF:

0.00213

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDH19-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.71

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

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