10-55353860-T-C

Variant summary

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

The ENST00000457975.2(ENSG00000236744):n.305+12232A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,912 control chromosomes in the GnomAD database, including 24,444 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 0.56 (24444 hom., cov: 32)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

Genes affected

(HGNC:):

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-155-187209A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000457975.2	n.305+12232A>G		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000613346.4	c.-155-187209A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84777 AN: 151794 Hom.: 24404 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.559 AC: 84879 AN: 151912 Hom.: 24444 Cov.: 32 AF XY: 0.554 AC XY: 41138 AN XY: 74228

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.540

Alfa AF: 0.504 Hom.: 8138

Bravo AF: 0.568

Asia WGS AF: 0.427 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.21
Dann	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1900493; hg19: chr10-57113620;