chr16-89194155-G-A

Variant names:

• chr16-89194155-G-A
• rs3785415
• NM_004933.3:c.2151+242G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 3

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004933.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH15	NM_004933.3	MANE Select	c.2151+242G>A		intron	N/A	NP_004924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH15	ENST00000289746.3	TSL:1 MANE Select	c.2151+242G>A		intron	N/A	ENSP00000289746.2

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

African (AFR) AF: 0.154 AC: 6402 AN: 41550

American (AMR) AF: 0.430 AC: 6579 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2307 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1897 AN: 5160

South Asian (SAS) AF: 0.421 AC: 2028 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5824 AN: 10606

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43372 AN: 67944

Other (OTH) AF: 0.532 AC: 1122 AN: 2108

Alfa AF: 0.600 Hom.: 55791

Bravo AF: 0.439

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.84
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3785415; hg19: chr16-89260563;