rs11004706

Positions:

• chr10-55053909-T-C

Variant summary

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

The NM_001354404.2(PCDH15):​c.-80+112667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 152,290 control chromosomes in the GnomAD database, including 574 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 0.070 (574 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-80+112667A>G		intron_variant			NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+112667A>G		intron_variant		5		ENSP00000394465
PCDH15	ENST00000613346.4	c.-80+112667A>G		intron_variant		4		ENSP00000481211

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10662 AN: 152172 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.00969

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0683

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

GnomAD4 genome AF: 0.0701 AC: 10680 AN: 152290 Hom.: 574 Cov.: 32 AF XY: 0.0680 AC XY: 5064 AN XY: 74484

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.00969

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0560 Hom.: 134

Bravo AF: 0.0733

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11004706; hg19: chr10-56813669;