16-89194155-G-A

Position:

• chr16-89194155-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004933.3(CDH15):​c.2151+242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,168 control chromosomes in the GnomAD database, including 19,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (19733 hom., cov: 34)
• Consequence: CDH15 NM_004933.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH15	NM_004933.3	c.2151+242G>A		intron_variant		ENST00000289746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH15	ENST00000289746.3	c.2151+242G>A		intron_variant		1	NM_004933.3	P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70423 AN: 152050 Hom.: 19741 Cov.: 34

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70403 AN: 152168 Hom.: 19733 Cov.: 34 AF XY: 0.458 AC XY: 34041 AN XY: 74388

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.532

Alfa AF: 0.615 Hom.: 39130

Bravo AF: 0.439

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.84

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: rs3785415; hg19: chr16-89260563;