16-68787043-G-A

Variant names:

Variant summary

Our verdict is . The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004360.5(CDH1):c.164-14627G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,086 control chromosomes in the GnomAD database, including 6,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). The gene CDH1 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.28 ( 6233 hom., cov: 32)

Consequence

CDH1
NM_004360.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.560

Publications

196 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
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: Unknown Classification: NO_KNOWN Submitted by: ClinGen

CDH1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004360.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for CDH1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-68787043-G-A is Benign according to our data. Variant chr16-68787043-G-A is described in ClinVar as Benign. ClinVar VariationId is 1623458.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH1	NM_004360.5	MANE Select	c.164-14627G>A	intron	N/A	NP_004351.1	A0A0U2ZQU7
CDH1	NM_001317184.2		c.164-14627G>A	intron	N/A	NP_001304113.1	P12830-2
CDH1	NM_001317185.2		c.-1452-14627G>A	intron	N/A	NP_001304114.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH1	ENST00000261769.10	TSL:1 MANE Select	c.164-14627G>A	intron	N/A	ENSP00000261769.4	P12830-1
CDH1	ENST00000422392.6	TSL:1	c.164-14627G>A	intron	N/A	ENSP00000414946.2	P12830-2
CDH1	ENST00000562836.5	TSL:1	n.235-14627G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43088

AN:

151968

Hom.:

6233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.295

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

GnomAD4 genome

AF:

0.283

AC:

43112

AN:

152086

Hom.:

6233

Cov.:

AF XY:

0.282

AC XY:

20940

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.296

AC:

12262

AN:

41470

American (AMR)

AF:

0.253

AC:

3870

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1374

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1077

AN:

5176

South Asian (SAS)

AF:

0.257

AC:

1236

AN:

4818

European-Finnish (FIN)

AF:

0.240

AC:

2537

AN:

10556

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19752

AN:

68000

Other (OTH)

AF:

0.293

AC:

619

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1625

3250

4876

6501

8126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.287

Hom.:

15875

Bravo

AF:

0.281

Asia WGS

AF:

0.282

AC:

982

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary diffuse gastric adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.48

(source)

DANN

Benign

0.62

PhyloP100

-0.56

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over