Variant chr16-89179547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_004933.3(CDH15):c.174C>T(p.His58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,607,280 control chromosomes in the GnomAD database, including 2,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.044 ( 261 hom., cov: 33)

Exomes 𝑓: 0.046 ( 2425 hom. )

Consequence

CDH15
NM_004933.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

CDH15 (HGNC:1754): (cadherin 15) This gene is a member of the cadherin superfamily of genes, encoding calcium-dependent intercellular adhesion glycoproteins. Cadherins consist of an extracellular domain containing 5 cadherin domains, a transmembrane region, and a conserved cytoplasmic domain. Transcripts from this particular cadherin are expressed in myoblasts and upregulated in myotubule-forming cells. The protein is thought to be essential for the control of morphogenetic processes, specifically myogenesis, and may provide a trigger for terminal muscle cell differentiation. [provided by RefSeq, Jul 2008]

CDH15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 16-89179547-C-T is Benign according to our data. Variant chr16-89179547-C-T is described in ClinVar as [Benign]. Clinvar id is 128645.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH15	NM_004933.3 linkuse as main transcript	c.174C>T	p.His58=	synonymous_variant	2/14	ENST00000289746.3	NP_004924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDH15	ENST00000289746.3 linkuse as main transcript	c.174C>T	p.His58=	synonymous_variant	2/14	1	NM_004933.3	ENSP00000289746	P1
CDH15	ENST00000521087.5 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	2/3	5
CDH15	ENST00000524089.1 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6660

AN:

152202

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00929

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.0349

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0379

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0635

AC:

15647

AN:

246492

Hom.:

889

AF XY:

0.0590

AC XY:

7865

AN XY:

133318

show subpopulations

Gnomad AFR exome

AF:

0.00872

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.00768

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.0249

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0384

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0461

AC:

67115

AN:

1454960

Hom.:

2425

Cov.:

AF XY:

0.0449

AC XY:

32494

AN XY:

723120

show subpopulations

Gnomad4 AFR exome

AF:

0.00778

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.00795

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.0389

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.0437

AC:

6664

AN:

152320

Hom.:

261

Cov.:

AF XY:

0.0489

AC XY:

3644

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00926

Gnomad4 AMR

AF:

0.0791

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.0348

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0379

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0363

Hom.:

129

Bravo

AF:

0.0421

Asia WGS

AF:

0.112

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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