16-68757767-CTCCTTCCTTCCT-CTCCTTCCT

Position:

• chr16-68757767-CTCCTTCCTTCCT-CTCCTTCCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004360.5(CDH1):​c.163+19378_163+19381delCCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (5979 hom., cov: 0)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.163+19378_163+19381delCCTT		intron_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.163+19378_163+19381delCCTT		intron_variant			NP_001304113.1
CDH1	NM_001317185.2	c.-1453+19378_-1453+19381delCCTT		intron_variant			NP_001304114.1
CDH1	NM_001317186.2	c.-1657+19378_-1657+19381delCCTT		intron_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.163+19357_163+19360delTCCT		intron_variant		1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.163+19357_163+19360delTCCT		intron_variant		1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.163+19357_163+19360delTCCT		intron_variant		1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.163+19357_163+19360delTCCT		intron_variant		5		ENSP00000458139.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 41693 AN: 147728 Hom.: 5974 Cov.: 0

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 41730 AN: 147844 Hom.: 5979 Cov.: 0 AF XY: 0.280 AC XY: 20088 AN XY: 71798

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs58548890; hg19: chr16-68791670;