Variant chr16-89179544-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004933.3(CDH15):c.171C>T(p.Asn57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,608,072 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 15 hom., cov: 33)

Exomes 𝑓: 0.014 ( 165 hom. )

Consequence

CDH15
NM_004933.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 16-89179544-C-T is Benign according to our data. Variant chr16-89179544-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128644.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BS2

High AC in GnomAd4 at 1703 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH15	NM_004933.3 linkuse as main transcript	c.171C>T	p.Asn57=	synonymous_variant	2/14	ENST00000289746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDH15	ENST00000289746.3 linkuse as main transcript	c.171C>T	p.Asn57=	synonymous_variant	2/14	1	NM_004933.3	P1
CDH15	ENST00000521087.5 linkuse as main transcript	n.236C>T		non_coding_transcript_exon_variant	2/3	5
CDH15	ENST00000524089.1 linkuse as main transcript	n.236C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1703

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.0115

AC:

2852

AN:

247022

Hom.:

AF XY:

0.0116

AC XY:

1550

AN XY:

133662

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00462

Gnomad ASJ exome

AF:

0.00237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0136

AC:

19749

AN:

1455756

Hom.:

165

Cov.:

AF XY:

0.0133

AC XY:

9588

AN XY:

723606

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.00475

Gnomad4 ASJ exome

AF:

0.00271

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00518

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.0112

AC:

1703

AN:

152316

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

875

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.0363

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.00843

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely 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

Likely 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

-0.36

CADD

Benign

8.7

DANN

Benign

0.77

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

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