dbSNP rs10516000: CDH19:c.195+51A>G (chr18-66571959-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021153.4(CDH19):c.195+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,351,144 control chromosomes in the GnomAD database, including 14,289 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 0.11 ( 1236 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13053 hom. )

Consequence

CDH19
NM_021153.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.244

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH19	NM_021153.4 link	c.195+51A>G		intron_variant	Intron 2 of 11	ENST00000262150.7	NP_066976.1	Q9H159-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH19	ENST00000262150.7 link	c.195+51A>G		intron_variant	Intron 2 of 11	1	NM_021153.4	ENSP00000262150.2		Q9H159-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16798

AN:

151608

Hom.:

1237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.137

AC:

27283

AN:

198924

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.00565

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.143

AC:

171062

AN:

1199418

Hom.:

13053

Cov.:

AF XY:

0.143

AC XY:

85108

AN XY:

596366

show subpopulations

African (AFR)

AF:

0.0214

AC:

586

AN:

27408

American (AMR)

AF:

0.197

AC:

6799

AN:

34578

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

2511

AN:

20094

East Asian (EAS)

AF:

0.00237

AC:

AN:

37568

South Asian (SAS)

AF:

0.132

AC:

8822

AN:

66842

European-Finnish (FIN)

AF:

0.178

AC:

8762

AN:

49254

Middle Eastern (MID)

AF:

0.138

AC:

673

AN:

4872

European-Non Finnish (NFE)

AF:

0.150

AC:

136244

AN:

908736

Other (OTH)

AF:

0.131

AC:

6576

AN:

50066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

7060

14121

21181

28242

35302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16798

AN:

151726

Hom.:

1236

Cov.:

AF XY:

0.110

AC XY:

8190

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.0278

AC:

1152

AN:

41496

American (AMR)

AF:

0.156

AC:

2362

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

440

AN:

3456

East Asian (EAS)

AF:

0.00484

AC:

AN:

5160

South Asian (SAS)

AF:

0.127

AC:

613

AN:

4826

European-Finnish (FIN)

AF:

0.174

AC:

1837

AN:

10580

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9961

AN:

67734

Other (OTH)

AF:

0.120

AC:

253

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

745

1490

2234

2979

3724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.140

Hom.:

955

Bravo

AF:

0.106

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

(source)

DANN

Benign

0.73

PhyloP100

-0.24

PromoterAI

-0.0069

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs10516000

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over