10-55335493-C-T

Position:

• chr10-55335493-C-T

Variant summary

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

The ENST00000457975.2(ENSG00000236744):​n.305+30599G>A 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 0.533 in 152,074 control chromosomes in the GnomAD database, including 21,975 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 0.53 (21975 hom., cov: 32)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-155-168842G>A		intron_variant			NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000457975.2	n.305+30599G>A		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000613346.4	c.-155-168842G>A		intron_variant		4		ENSP00000481211

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80990 AN: 151956 Hom.: 21944 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.533 AC: 81081 AN: 152074 Hom.: 21975 Cov.: 32 AF XY: 0.528 AC XY: 39279 AN XY: 74346

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.521

Alfa AF: 0.531 Hom.: 4385

Bravo AF: 0.539

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1900472; hg19: chr10-57095253;