16-68757767-CTCCTTCCTTCCT-CTCCTTCCTTCCTTCCT

Position:

• chr16-68757767-CTCCTTCCTTCCT-CTCCTTCCTTCCTTCCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004360.5(CDH1):​c.163+19378_163+19381dupCCTT 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 0.0086 (16 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.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00863 (1277/148014) while in subpopulation EAS AF= 0.0487 (243/4986). AF 95% confidence interval is 0.0437. There are 16 homozygotes in gnomad4. There are 659 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1277 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.163+19378_163+19381dupCCTT		intron_variant		1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.163+19378_163+19381dupCCTT		intron_variant		1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.163+19378_163+19381dupCCTT		intron_variant		1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.163+19378_163+19381dupCCTT		intron_variant		5		ENSP00000458139.1

Frequencies

GnomAD3 genomes AF: 0.00863 AC: 1277 AN: 147896 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00333

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00127

Gnomad OTH AF: 0.00842

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

GnomAD4 genome AF: 0.00863 AC: 1277 AN: 148014 Hom.: 16 Cov.: 0 AF XY: 0.00917 AC XY: 659 AN XY: 71876

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0206

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00127

Gnomad4 OTH AF: 0.00784

ClinVar

Not reported in ClinVar

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: rs58548890; hg19: chr16-68791670;