rs17690554

Variant names:

• chr16-68835607-C-G
• rs17690554
• NM_004360.5:c.*2108C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-68835607-C-G
• chr16-68835607-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004360.5(CDH1):​c.*2108C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 175,164 control chromosomes in the GnomAD database, including 2,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2174 hom., cov: 32)
  • Exomes 𝑓: 0.17 (322 hom.)
• Consequence: CDH1 NM_004360.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 14 publications found

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]

CDH1 Gene-Disease associations (from GenCC):

• blepharocheilodontic syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P
• CDH1-related diffuse gastric and lobular breast cancer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• hereditary diffuse gastric adenocarcinoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• cleft soft palate

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• orofacial cleft 3

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• blepharocheilodontic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH1	NM_004360.5	c.*2108C>G		downstream_gene_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.*2108C>G		downstream_gene_variant			NP_001304113.1
CDH1	NM_001317185.2	c.*2108C>G		downstream_gene_variant			NP_001304114.1
CDH1	NM_001317186.2	c.*2108C>G		downstream_gene_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.*2108C>G		downstream_gene_variant		1	NM_004360.5	ENSP00000261769.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25879 AN: 152024 Hom.: 2170 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.166 AC: 3816 AN: 23022 Hom.: 322 AF XY: 0.165 AC XY: 1753 AN XY: 10646

African (AFR) AF: 0.163 AC: 120 AN: 738

American (AMR) AF: 0.167 AC: 81 AN: 484

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 247 AN: 1424

East Asian (EAS) AF: 0.132 AC: 662 AN: 5030

South Asian (SAS) AF: 0.0638 AC: 12 AN: 188

European-Finnish (FIN) AF: 0.212 AC: 92 AN: 434

Middle Eastern (MID) AF: 0.115 AC: 17 AN: 148

European-Non Finnish (NFE) AF: 0.178 AC: 2269 AN: 12780

Other (OTH) AF: 0.176 AC: 316 AN: 1796

GnomAD4 genome AF: 0.170 AC: 25923 AN: 152142 Hom.: 2174 Cov.: 32 AF XY: 0.169 AC XY: 12589 AN XY: 74366

African (AFR) AF: 0.145 AC: 6037 AN: 41528

American (AMR) AF: 0.167 AC: 2560 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.156 AC: 802 AN: 5156

South Asian (SAS) AF: 0.109 AC: 524 AN: 4824

European-Finnish (FIN) AF: 0.207 AC: 2188 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12760 AN: 67996

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.0877 Hom.: 120

Bravo AF: 0.170

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17690554; hg19: chr16-68869510;