rs1935468

Positions:

• chr10-54323965-T-C

Variant summary

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

The NM_033056.4(PCDH15):​c.705+5631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,980 control chromosomes in the GnomAD database, including 38,583 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 0.71 (38583 hom., cov: 32)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

Genes affected

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 = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.705+5631A>G		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.705+5631A>G		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.705+5631A>G		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.705+5631A>G		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107131 AN: 151862 Hom.: 38543 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.706 AC: 107231 AN: 151980 Hom.: 38583 Cov.: 32 AF XY: 0.698 AC XY: 51825 AN XY: 74262

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.727

Alfa AF: 0.717 Hom.: 17894

Bravo AF: 0.707

Asia WGS AF: 0.441 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.050
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1935468; hg19: chr10-56083725;