10-54062675-T-C

Position:

• chr10-54062675-T-C

Variant summary

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

The ENST00000320301.11(PCDH15):​c.2220+4082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,364 control chromosomes in the GnomAD database, including 12,408 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 0.40 (12408 hom., cov: 31)
• Consequence: PCDH15 ENST00000320301.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.2220+4082A>G		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.2220+4082A>G		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.2220+4082A>G		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.2220+4082A>G		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60104 AN: 151246 Hom.: 12404 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.397 AC: 60133 AN: 151364 Hom.: 12408 Cov.: 31 AF XY: 0.395 AC XY: 29162 AN XY: 73896

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.437

Alfa AF: 0.428 Hom.: 6090

Bravo AF: 0.398

Asia WGS AF: 0.241 AC: 836 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.3
DANN	Benign	0.80

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: rs7079133; hg19: chr10-55822435;