rs2050545

chr10-54743717-C-T

Variant summary

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

The NM_033056.4(PCDH15):c.-29+57208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 151,884 control chromosomes in the GnomAD database, including 56,437 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 0.86 (56437 hom., cov: 30)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.-29+57208G>A		intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.-29+57208G>A		intron_variant		ENST00000320301.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.-29+57208G>A		intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.-29+57208G>A		intron_variant			NM_001384140.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130053 AN: 151770 Hom.: 56415 Cov.: 30

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.857 AC: 130116 AN: 151884 Hom.: 56437 Cov.: 30 AF XY: 0.850 AC XY: 63111 AN XY: 74248

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.861

Alfa AF: 0.907 Hom.: 111179

Bravo AF: 0.843

Asia WGS AF: 0.652 AC: 2267 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.9
Dann	Benign	0.42

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: rs2050545; hg19: chr10-56503477;