16-89179544-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (15 hom., cov: 33)
  • Exomes 𝑓: 0.014 (165 hom.)
• Consequence: CDH15 NM_004933.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Benign. Variant got -8 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 no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.55 with no splicing effect.
• BS2: High AC in GnomAd at 1703 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1703 AN: 152198 Hom.: 15 Cov.: 33

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.: 33 AF XY: 0.0116 AC XY: 1550 AN XY: 133662

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.: 32 AF XY: 0.0133 AC XY: 9588 AN XY: 723606

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.: 15 Cov.: 33 AF XY: 0.0117 AC XY: 875 AN XY: 74494

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.: 4

Bravo AF: 0.00843

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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. -

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

Other links and lift over

dbSNP: rs148798647; hg19: chr16-89245952;