10-55049046-T-C

Position:

• chr10-55049046-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+117530A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,700 control chromosomes in the GnomAD database, including 23,134 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 0.54 (23134 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-80+117530A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+117530A>G		intron_variant		5
PCDH15	ENST00000613346.4	c.-80+117530A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82398 AN: 151582 Hom.: 23122 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.543 AC: 82449 AN: 151700 Hom.: 23134 Cov.: 32 AF XY: 0.548 AC XY: 40622 AN XY: 74120

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.538

Alfa AF: 0.574 Hom.: 13268

Bravo AF: 0.529

Asia WGS AF: 0.628 AC: 2180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10763176; hg19: chr10-56808806;