rs1922166

chr10-55035318-C-Achr10-55035318-C-Gchr10-55035318-C-T

Variant summary

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

The NM_001354404.2(PCDH15):c.-80+131258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,824 control chromosomes in the GnomAD database, including 25,066 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 0.57 (25066 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-80+131258G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+131258G>T		intron_variant		5
PCDH15	ENST00000613346.4	c.-80+131258G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86603 AN: 151706 Hom.: 25045 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.571 AC: 86672 AN: 151824 Hom.: 25066 Cov.: 32 AF XY: 0.575 AC XY: 42651 AN XY: 74182

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.559

Alfa AF: 0.578 Hom.: 45250

Bravo AF: 0.560

Asia WGS AF: 0.637 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.24
Dann	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1922166; hg19: chr10-56795078;