rs10740609

chr10-55031209-T-Achr10-55031209-T-Cchr10-55031209-T-G

Variant summary

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

The NM_001354404.2(PCDH15):c.-79-133709A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,168 control chromosomes in the GnomAD database, including 50,232 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 0.81 (50232 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-79-133709A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000458638.1	c.-79-133709A>T		intron_variant		5
PCDH15	ENST00000613346.4	c.-79-133709A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123131 AN: 152050 Hom.: 50174 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.810 AC: 123250 AN: 152168 Hom.: 50232 Cov.: 32 AF XY: 0.815 AC XY: 60586 AN XY: 74368

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.810

Alfa AF: 0.769 Hom.: 25073

Bravo AF: 0.808

Asia WGS AF: 0.868 AC: 3017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10740609; hg19: chr10-56790969;