rs1900482

chr10-55348435-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+17657G>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 0.542 in 151,814 control chromosomes in the GnomAD database, including 22,774 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 0.54 (22774 hom., cov: 32)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-155-181784G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000457975.2	n.305+17657G>A		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000613346.4	c.-155-181784G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82173 AN: 151696 Hom.: 22738 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.542 AC: 82270 AN: 151814 Hom.: 22774 Cov.: 32 AF XY: 0.538 AC XY: 39899 AN XY: 74206

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.523

Alfa AF: 0.511 Hom.: 33025

Bravo AF: 0.549

Asia WGS AF: 0.422 AC: 1469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.47
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: rs1900482; hg19: chr10-57108195;