16-68757767-CTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr16-68757767-C-CTCCTTCCT
• rs58548890
• NM_004360.5:c.163+19374_163+19381dupCCTTCCTT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_004360.5(CDH1):​c.163+19374_163+19381dupCCTTCCTT 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 0.000074 (0 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 Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH1	NM_004360.5	c.163+19374_163+19381dupCCTTCCTT		intron_variant	Intron 2 of 15	ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.163+19374_163+19381dupCCTTCCTT		intron_variant	Intron 2 of 14		NP_001304113.1
CDH1	NM_001317185.2	c.-1453+19374_-1453+19381dupCCTTCCTT		intron_variant	Intron 2 of 15		NP_001304114.1
CDH1	NM_001317186.2	c.-1657+19374_-1657+19381dupCCTTCCTT		intron_variant	Intron 2 of 14		NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.163+19356_163+19357insTCCTTCCT		intron_variant	Intron 2 of 15	1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.163+19356_163+19357insTCCTTCCT		intron_variant	Intron 2 of 14	1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.163+19356_163+19357insTCCTTCCT		intron_variant	Intron 2 of 14	1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.163+19356_163+19357insTCCTTCCT		intron_variant	Intron 2 of 14	5		ENSP00000458139.1

Frequencies

GnomAD3 genomes AF: 0.0000744 AC: 11 AN: 147918 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000744 AC: 11 AN: 147918 Hom.: 0 Cov.: 0 AF XY: 0.0000697 AC XY: 5 AN XY: 71764

Gnomad4 AFR AF: 0.000150

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000216

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000447

Gnomad4 OTH AF: 0.00

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;