chr18-66571959-T-C

Variant names:

• chr18-66571959-T-C
• rs10516000
• NM_021153.4:c.195+51A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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]

ACMG classification

Verdict is Benign. Variant got -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	c.195+51A>G		intron_variant	Intron 2 of 11	ENST00000262150.7	NP_066976.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16798 AN: 151608 Hom.: 1237 Cov.: 32

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

GnomAD3 exomes AF: 0.137 AC: 27283 AN: 198924 Hom.: 2243 AF XY: 0.139 AC XY: 14913 AN XY: 107318

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 SAS exome AF: 0.130

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.: 15 AF XY: 0.143 AC XY: 85108 AN XY: 596366

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00237

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.111 AC: 16798 AN: 151726 Hom.: 1236 Cov.: 32 AF XY: 0.110 AC XY: 8190 AN XY: 74158

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.120

Alfa AF: 0.140 Hom.: 865

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
DANN	Benign	0.73

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: rs10516000; hg19: chr18-64239196;