rs7188750

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 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

CDH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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
CDH1	NM_004360.5 link	c.687+144G>A	intron_variant	Intron 5 of 15	ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2 link	c.687+144G>A	intron_variant	Intron 5 of 14		NP_001304113.1
CDH1	NM_001317185.2 link	c.-929+144G>A	intron_variant	Intron 5 of 15		NP_001304114.1
CDH1	NM_001317186.2 link	c.-1133+144G>A	intron_variant	Intron 5 of 14		NP_001304115.1

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

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

African (AFR)

AF:

0.362

AC:

5897

AN:

16280

American (AMR)

AF:

0.186

AC:

5924

AN:

31812

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

2940

AN:

19450

East Asian (EAS)

AF:

0.132

AC:

4315

AN:

32716

South Asian (SAS)

AF:

0.130

AC:

7899

AN:

60696

European-Finnish (FIN)

AF:

0.184

AC:

6296

AN:

34280

Middle Eastern (MID)

AF:

0.123

AC:

305

AN:

2470

European-Non Finnish (NFE)

AF:

0.164

AC:

62292

AN:

380616

Other (OTH)

AF:

0.174

AC:

5613

AN:

32208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

4222

8444

12665

16887

21109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33763

AN:

152104

Hom.:

4383

Cov.:

AF XY:

0.219

AC XY:

16255

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.367

AC:

15218

AN:

41466

American (AMR)

AF:

0.190

AC:

2905

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

538

AN:

3468

East Asian (EAS)

AF:

0.156

AC:

806

AN:

5180

South Asian (SAS)

AF:

0.126

AC:

609

AN:

4816

European-Finnish (FIN)

AF:

0.177

AC:

1871

AN:

10596

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11301

AN:

67984

Other (OTH)

AF:

0.186

AC:

393

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1246

2492

3738

4984

6230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

2961

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

(source)

DANN

Benign

0.89

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over