16-68757767-CTCCTTCCTTCCT-CTCCT

Position:

• chr16-68757767-CTCCTTCCTTCCT-CTCCT

Variant summary

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

The NM_004360.5(CDH1):​c.163+19374_163+19381delCCTTCCTT 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 0.0039 (1 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 afr. gnomad4 allele frequency = 0.00388 (574/148034) while in subpopulation AFR AF= 0.0127 (509/40182). AF 95% confidence interval is 0.0118. There are 1 homozygotes in gnomad4. There are 287 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.163+19374_163+19381delCCTTCCTT		intron_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.163+19374_163+19381delCCTTCCTT		intron_variant			NP_001304113.1
CDH1	NM_001317185.2	c.-1453+19374_-1453+19381delCCTTCCTT		intron_variant			NP_001304114.1
CDH1	NM_001317186.2	c.-1657+19374_-1657+19381delCCTTCCTT		intron_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.163+19374_163+19381delCCTTCCTT		intron_variant		1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.163+19374_163+19381delCCTTCCTT		intron_variant		1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.163+19374_163+19381delCCTTCCTT		intron_variant		1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.163+19374_163+19381delCCTTCCTT		intron_variant		5		ENSP00000458139.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 574 AN: 147916 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00171

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.000647

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000372

Gnomad OTH AF: 0.00396

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

GnomAD4 genome AF: 0.00388 AC: 574 AN: 148034 Hom.: 1 Cov.: 0 AF XY: 0.00399 AC XY: 287 AN XY: 71890

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00171

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000647

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000372

Gnomad4 OTH AF: 0.00441

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;