rs2441760

chr10-55317875-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+48217G>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 0.741 in 152,046 control chromosomes in the GnomAD database, including 42,580 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 0.74 (42580 hom., cov: 32)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-155-151224G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000457975.2	n.305+48217G>A		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000458638.1	c.-156+1724G>A		intron_variant		5
PCDH15	ENST00000613346.4	c.-155-151224G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112630 AN: 151926 Hom.: 42533 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.741 AC: 112742 AN: 152046 Hom.: 42580 Cov.: 32 AF XY: 0.736 AC XY: 54744 AN XY: 74336

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.725

Alfa AF: 0.732 Hom.: 54530

Bravo AF: 0.746

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.31
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2441760; hg19: chr10-57077635;