chr16-68644981-G-C

Position:

• chr16-68644981-G-C

Variant summary

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

The ENST00000562172.2(CDH3-AS1):​n.949C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 284,740 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (34 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (32 hom.)
• Consequence: CDH3-AS1 ENST00000562172.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400

Genes affected

CDH3-AS1 (HGNC:56084): (CDH3 antisense RNA 1)

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-68644981-G-C is Benign according to our data. Variant chr16-68644981-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 320213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH3-AS1	ENST00000562172.2	n.949C>G		non_coding_transcript_exon_variant	2/2	3
CDH3	ENST00000565453.1	n.223-28G>C		intron_variant, non_coding_transcript_variant		4
CDH3	ENST00000429102.6			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00698 AC: 1062 AN: 152212 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00927

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00530 AC: 702 AN: 132410 Hom.: 32 Cov.: 0 AF XY: 0.00493 AC XY: 341 AN XY: 69238

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.0782

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00976

Gnomad4 SAS exome AF: 0.000654

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000501

Gnomad4 OTH exome AF: 0.00691

GnomAD4 genome AF: 0.00695 AC: 1059 AN: 152330 Hom.: 34 Cov.: 33 AF XY: 0.00776 AC XY: 578 AN XY: 74492

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00929

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.000420 Hom.: 0

Bravo AF: 0.0126

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

EEM syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs74674351; hg19: chr16-68678884;