10-55214430-T-C

Variant names:

• chr10-55214430-T-C
• rs11004778
• NM_001354404.2:c.-155-47779A>G

Variant summary

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

The NM_001354404.2(PCDH15):​c.-155-47779A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,846 control chromosomes in the GnomAD database, including 5,402 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 0.26 (5402 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-155-47779A>G		intron_variant	Intron 2 of 34		NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000458638.1	c.-155-47779A>G		intron_variant	Intron 1 of 5	5		ENSP00000394465.1
PCDH15	ENST00000613346.4	c.-155-47779A>G		intron_variant	Intron 2 of 5	4		ENSP00000481211.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39433 AN: 151728 Hom.: 5402 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.260 AC: 39434 AN: 151846 Hom.: 5402 Cov.: 32 AF XY: 0.261 AC XY: 19371 AN XY: 74252

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.290

Alfa AF: 0.289 Hom.: 10643

Bravo AF: 0.255

Asia WGS AF: 0.238 AC: 825 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11004778; hg19: chr10-56974190;