10-54444531-G-T

Variant names:

• chr10-54444531-G-T
• rs7476422
• NM_033056.4:c.158-65589C>A

Variant summary

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

The NM_001384140.1(PCDH15):​c.158-65589C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,522 control chromosomes in the GnomAD database, including 40,414 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 0.72 (40414 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.158-65589C>A		intron_variant	Intron 3 of 32	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.158-65589C>A		intron_variant	Intron 3 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.158-65589C>A		intron_variant	Intron 3 of 32	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.158-65589C>A		intron_variant	Intron 3 of 37		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 108874 AN: 151404 Hom.: 40372 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.719 AC: 108966 AN: 151522 Hom.: 40414 Cov.: 32 AF XY: 0.708 AC XY: 52425 AN XY: 74040

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.738

Alfa AF: 0.728 Hom.: 80983

Bravo AF: 0.719

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.36

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: rs7476422; hg19: chr10-56204291;