dbSNP rs7188750: CDH1:c.687+144G>A (chr16-68808992-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004360.5(CDH1):c.687+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 762,632 control chromosomes in the GnomAD database, including 13,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4383 hom., cov: 32)

Exomes 𝑓: 0.17 ( 9109 hom. )

Consequence

CDH1
NM_004360.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.619

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-68808992-G-A is Benign according to our data. Variant chr16-68808992-G-A is described in ClinVar as [Benign]. Clinvar id is 1259545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDH1	NM_004360.5 link	c.687+144G>A	intron_variant	Intron 5 of 15	ENST00000261769.10	NP_004351.1	P12830-1A0A0U2ZQU7B3GN61
CDH1	NM_001317184.2 link	c.687+144G>A	intron_variant	Intron 5 of 14		NP_001304113.1	P12830-2B3GN61
CDH1	NM_001317185.2 link	c.-929+144G>A	intron_variant	Intron 5 of 15		NP_001304114.1	P12830B3GN61Q9UII7
CDH1	NM_001317186.2 link	c.-1133+144G>A	intron_variant	Intron 5 of 14		NP_001304115.1	P12830B3GN61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10 link	c.687+144G>A		intron_variant	Intron 5 of 15	1	NM_004360.5	ENSP00000261769.4		P12830-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33701

AN:

151986

Hom.:

4368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.166

AC:

101481

AN:

610528

Hom.:

9109

Cov.:

AF XY:

0.163

AC XY:

52989

AN XY:

325668

show subpopulations

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.222

AC:

33763

AN:

152104

Hom.:

4383

Cov.:

AF XY:

0.219

AC XY:

16255

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.179

Hom.:

1921

Bravo

AF:

0.230

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.2

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over