8-94130944-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004063.4(CDH17):c.2216A>C(p.Glu739Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,604,310 control chromosomes in the GnomAD database, including 237,689 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18585 hom., cov: 31)

Exomes 𝑓: 0.54 ( 219104 hom. )

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.369

Publications

42 publications found

Variant links:

Genes affected

CDH17 (HGNC:1756): (cadherin 17) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

CDH17 links:

ENSG00000304524 (HGNC:):

ENSG00000304524 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 (MetaRNN=4.781197E-5).

BP6

Variant 8-94130944-T-G is Benign according to our data. Variant chr8-94130944-T-G is described in ClinVar as Benign. ClinVar VariationId is 1287378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH17	NM_004063.4 link	c.2216A>C	p.Glu739Ala	missense_variant	Exon 16 of 18	ENST00000027335.8	NP_004054.3	Q12864

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8 link	c.2216A>C	p.Glu739Ala	missense_variant	Exon 16 of 18	1	NM_004063.4	ENSP00000027335.3		Q12864

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72572

AN:

151626

Hom.:

18594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.447

GnomAD2 exomes

AF:

0.512

AC:

128225

AN:

250280

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.544

AC:

790675

AN:

1452568

Hom.:

219104

Cov.:

AF XY:

0.543

AC XY:

392771

AN XY:

723090

show subpopulations

African (AFR)

AF:

0.295

AC:

9822

AN:

33332

American (AMR)

AF:

0.406

AC:

18083

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

14601

AN:

26044

East Asian (EAS)

AF:

0.532

AC:

21097

AN:

39652

South Asian (SAS)

AF:

0.467

AC:

40104

AN:

85940

European-Finnish (FIN)

AF:

0.609

AC:

32435

AN:

53298

Middle Eastern (MID)

AF:

0.415

AC:

2386

AN:

5750

European-Non Finnish (NFE)

AF:

0.563

AC:

620987

AN:

1103866

Other (OTH)

AF:

0.518

AC:

31160

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

15470

30941

46411

61882

77352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17090

34180

51270

68360

85450

<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:

0.478

AC:

72582

AN:

151742

Hom.:

18585

Cov.:

AF XY:

0.477

AC XY:

35318

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.306

AC:

12671

AN:

41368

American (AMR)

AF:

0.415

AC:

6329

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

1925

AN:

3468

East Asian (EAS)

AF:

0.549

AC:

2812

AN:

5120

South Asian (SAS)

AF:

0.476

AC:

2287

AN:

4808

European-Finnish (FIN)

AF:

0.613

AC:

6433

AN:

10490

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.567

AC:

38540

AN:

67918

Other (OTH)

AF:

0.449

AC:

946

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1853

3706

5558

7411

9264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.536

Hom.:

92325

Bravo

AF:

0.455

TwinsUK

AF:

0.561

AC:

2081

ALSPAC

AF:

0.551

AC:

2124

ESP6500AA

AF:

0.308

AC:

1359

ESP6500EA

AF:

0.558

AC:

4801

ExAC

AF:

0.512

AC:

62133

Asia WGS

AF:

0.495

AC:

1720

AN:

3478

EpiCase

AF:

0.554

EpiControl

AF:

0.550

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

- -

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23326130) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.5

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.45

.;T;T

MetaRNN

Benign

0.000048

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

L;.;L

PhyloP100

0.37

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.062

MPC

0.070

ClinPred

0.0048

GERP RS

0.45

Varity_R

0.028

gMVP

0.61

Mutation Taster

=98/2

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

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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