16-68644735-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000562172.2(CDH3-AS1):n.1194_1195insT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (24819 hom., cov: 0)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: CDH3-AS1 ENST00000562172.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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 -10 ACMG points.

• BP6: Variant 16-68644735-C-CA is Benign according to our data. Variant chr16-68644735-C-CA is described in ClinVar as [Benign]. Clinvar id is 320206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 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.1194_1195insT		non_coding_transcript_exon_variant	2/2	3
CDH3	ENST00000565453.1	n.223-258dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 79202 AN: 127042 Hom.: 24821 Cov.: 0

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.305 AC: 75 AN: 246 Hom.: 0 Cov.: 0 AF XY: 0.299 AC XY: 40 AN XY: 134

Gnomad4 AMR exome AF: 0.333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.623 AC: 79186 AN: 127034 Hom.: 24819 Cov.: 0 AF XY: 0.622 AC XY: 37569 AN XY: 60408

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.635

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

EEM syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11440411; hg19: chr16-68678638;