10-55343600-A-G

Variant summary

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

The ENST00000457975.2(ENSG00000236744):n.305+22492T>C 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 0.551 in 151,472 control chromosomes in the GnomAD database, including 23,534 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 0.55 (23534 hom., cov: 30)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-155-176949T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000457975.2	n.305+22492T>C		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000613346.4	c.-155-176949T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83381 AN: 151352 Hom.: 23498 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.551 AC: 83481 AN: 151472 Hom.: 23534 Cov.: 30 AF XY: 0.546 AC XY: 40408 AN XY: 73962

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.532

Alfa AF: 0.545 Hom.: 2936

Bravo AF: 0.559

Asia WGS AF: 0.425 AC: 1478 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.22
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2218582; hg19: chr10-57103360;