10-54668517-C-T

Position:

• chr10-54668517-C-T

Variant summary

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

The ENST00000320301.11(PCDH15):​c.-28-4227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,930 control chromosomes in the GnomAD database, including 10,614 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 0.36 (10614 hom., cov: 32)
• Consequence: PCDH15 ENST00000320301.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.-28-4227G>A		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.-28-4227G>A		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.-28-4227G>A		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.-28-4227G>A		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55148 AN: 151812 Hom.: 10591 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.363 AC: 55219 AN: 151930 Hom.: 10614 Cov.: 32 AF XY: 0.358 AC XY: 26544 AN XY: 74238

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.377

Alfa AF: 0.329 Hom.: 17092

Bravo AF: 0.382

Asia WGS AF: 0.277 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.9
DANN	Benign	0.71

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: rs7902184; hg19: chr10-56428277;