dbSNP rs7194373: CDH13:c.45+12348T>G (chr16-82639485-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001257.5(CDH13):c.45+12348T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,476,718 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 202 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 175 hom. )

Consequence

CDH13
NM_001257.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.569

Publications

0 publications found

Variant links:

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

CDH13 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=-0.87).

BP6

Variant 16-82639485-T-G is Benign according to our data. Variant chr16-82639485-T-G is described in ClinVar as Benign. ClinVar VariationId is 257646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5 link	c.45+12348T>G		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1	P55290-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6 link	c.45+12348T>G		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1		P55290-1

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4234

AN:

152196

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0181

GnomAD2 exomes

AF:

0.00613

AC:

787

AN:

128330

AF XY:

0.00498

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.00563

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.00305

AC:

4045

AN:

1324404

Hom.:

175

Cov.:

AF XY:

0.00270

AC XY:

1771

AN XY:

656870

show subpopulations

African (AFR)

AF:

0.100

AC:

3063

AN:

30614

American (AMR)

AF:

0.00660

AC:

235

AN:

35622

Ashkenazi Jewish (ASJ)

AF:

0.00133

AC:

AN:

24792

East Asian (EAS)

AF:

0.00

AC:

AN:

35432

South Asian (SAS)

AF:

0.000295

AC:

AN:

78026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33432

Middle Eastern (MID)

AF:

0.00501

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

0.000201

AC:

206

AN:

1025014

Other (OTH)

AF:

0.00818

AC:

457

AN:

55880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

168

336

505

673

841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.0279

AC:

4249

AN:

152314

Hom.:

202

Cov.:

AF XY:

0.0268

AC XY:

1995

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0953

AC:

3959

AN:

41556

American (AMR)

AF:

0.0136

AC:

208

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00166

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68030

Other (OTH)

AF:

0.0180

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

197

394

592

789

986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0124

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.47

(source)

DANN

Benign

0.54

PhyloP100

-0.57

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

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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