rs1057517618

Positions:

• chr16-68738281-C-A
• chr16-68738281-C-G
• chr16-68738281-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004360.5(CDH1):​c.49-16C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CDH1 NM_004360.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-68738281-C-A is Benign according to our data. Variant chr16-68738281-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2796242.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001304113.1
CDH1	NM_001317185.2	c.-1567-16C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001304114.1
CDH1	NM_001317186.2	c.-1771-16C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004360.5	ENSP00000261769	P1
CDH1	ENST00000422392.6	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000414946
CDH1	ENST00000566612.5	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1		ENSP00000454782
CDH1	ENST00000566510.5	c.49-16C>A		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000458139

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362704 Hom.: 0 Cov.: 26 AF XY: 0.00000148 AC XY: 1 AN XY: 674502

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.56e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary diffuse gastric adenocarcinoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-68772184;