16-68737515-C-CGCCCCAGCCCCGT

Position:

• chr16-68737515-C-CGCCCCAGCCCCGT

Variant summary

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

The ENST00000261769.10(CDH1):​c.48+62_48+63insCGTGCCCCAGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,350,920 control chromosomes in the GnomAD database, including 490,647 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (47790 hom., cov: 0)
  • Exomes 𝑓: 0.85 (442857 hom.)
• Consequence: CDH1 ENST00000261769.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.554

Genes affected

CDH1 (HGNC:1748): (cadherin 1) 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. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-68737515-C-CGCCCCAGCCCCGT is Benign according to our data. Variant chr16-68737515-C-CGCCCCAGCCCCGT is described in ClinVar as [Benign]. Clinvar id is 1243608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant			NP_001304113.1
CDH1	NM_001317185.2	c.-1568+62_-1568+63insCGTGCCCCAGCCC		intron_variant			NP_001304114.1
CDH1	NM_001317186.2	c.-1772+62_-1772+63insCGTGCCCCAGCCC		intron_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant		1	NM_004360.5	ENSP00000261769	P1
CDH1	ENST00000422392.6	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant		1		ENSP00000414946
CDH1	ENST00000566612.5	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant, NMD_transcript_variant		1		ENSP00000454782
CDH1	ENST00000566510.5	c.48+62_48+63insCGTGCCCCAGCCC		intron_variant, NMD_transcript_variant		5		ENSP00000458139

Frequencies

GnomAD3 genomes AF: 0.807 AC: 119287 AN: 147756 Hom.: 47776 Cov.: 0

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.821

GnomAD3 exomes AF: 0.811 AC: 95708 AN: 118050 Hom.: 39761 AF XY: 0.815 AC XY: 53357 AN XY: 65452

Gnomad AFR exome AF: 0.640

Gnomad AMR exome AF: 0.736

Gnomad ASJ exome AF: 0.912

Gnomad EAS exome AF: 0.760

Gnomad SAS exome AF: 0.775

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.870

Gnomad OTH exome AF: 0.843

GnomAD4 exome AF: 0.851 AC: 1023448 AN: 1203070 Hom.: 442857 AF XY: 0.849 AC XY: 511399 AN XY: 602006

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.761

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.827

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.842

GnomAD4 genome AF: 0.807 AC: 119342 AN: 147850 Hom.: 47790 Cov.: 0 AF XY: 0.804 AC XY: 58119 AN XY: 72316

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.819

Alfa AF: 0.804 Hom.: 4921

Asia WGS AF: 0.775 AC: 2696 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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: rs45625236; hg19: chr16-68771418;