10-54448976-G-A

Position:

• chr10-54448976-G-A

Variant summary

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

The NM_001384140.1(PCDH15):​c.158-70034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,470 control chromosomes in the GnomAD database, including 21,083 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 0.50 (21083 hom., cov: 31)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.158-70034C>T		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.158-70034C>T		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.158-70034C>T		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.158-70034C>T		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75619 AN: 151352 Hom.: 21079 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.499 AC: 75654 AN: 151470 Hom.: 21083 Cov.: 31 AF XY: 0.495 AC XY: 36645 AN XY: 73984

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.540

Alfa AF: 0.601 Hom.: 34617

Bravo AF: 0.493

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0090
DANN	Benign	0.38

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: rs2026414; hg19: chr10-56208736;