10-55024936-G-T

Variant names:

• chr10-55024936-G-T
• rs11004683
• NM_001354404.2:c.-79-127436C>A

Variant summary

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

The NM_001354404.2(PCDH15):​c.-79-127436C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,720 control chromosomes in the GnomAD database, including 24,901 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 (24901 hom., cov: 31)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

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 (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-79-127436C>A		intron_variant	Intron 3 of 34		NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000458638.1	c.-79-127436C>A		intron_variant	Intron 2 of 5	5		ENSP00000394465.1
PCDH15	ENST00000613346.4	c.-79-127436C>A		intron_variant	Intron 3 of 5	4		ENSP00000481211.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86300 AN: 151606 Hom.: 24881 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.491

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: 0.569 AC: 86368 AN: 151720 Hom.: 24901 Cov.: 31 AF XY: 0.573 AC XY: 42503 AN XY: 74130

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.559

Alfa AF: 0.571 Hom.: 3052

Bravo AF: 0.558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11004683; hg19: chr10-56784696;