Variant chr16-89179526-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004933.3(CDH15):c.153G>A(p.Pro51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,612,142 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 74 hom. )

Consequence

CDH15
NM_004933.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.768

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 16-89179526-G-A is Benign according to our data. Variant chr16-89179526-G-A is described in ClinVar as [Benign]. Clinvar id is 128643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.768 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 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.153G>A	p.Pro51=	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.153G>A	p.Pro51=	synonymous_variant	2/14	1	NM_004933.3	ENSP00000289746	P1
CDH15	ENST00000521087.5 linkuse as main transcript	n.218G>A		non_coding_transcript_exon_variant	2/3	5
CDH15	ENST00000524089.1 linkuse as main transcript	n.218G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2698

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00463

AC:

1154

AN:

249190

Hom.:

AF XY:

0.00353

AC XY:

476

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.00300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00175

AC:

2556

AN:

1459828

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1098

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.00375

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.00398

GnomAD4 genome

AF:

0.0178

AC:

2704

AN:

152314

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1272

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0613

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00907

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 23, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.9

DANN

Benign

0.74

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