10-55349557-A-T

Position:

• chr10-55349557-A-T

Variant summary

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

The ENST00000457975.2(ENSG00000236744):​n.305+16535T>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,798 control chromosomes in the GnomAD database, including 24,436 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 0.56 (24436 hom., cov: 30)
• Consequence: ENST00000457975.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

Genes affected

(HGNC:):

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-155-182906T>A		intron_variant			NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000457975.2	n.305+16535T>A		intron_variant, non_coding_transcript_variant		3
PCDH15	ENST00000613346.4	c.-155-182906T>A		intron_variant		4		ENSP00000481211

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84726 AN: 151676 Hom.: 24396 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.559 AC: 84829 AN: 151798 Hom.: 24436 Cov.: 30 AF XY: 0.554 AC XY: 41120 AN XY: 74196

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.538

Alfa AF: 0.551 Hom.: 2909

Bravo AF: 0.568

Asia WGS AF: 0.428 AC: 1489 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.81
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10825499; hg19: chr10-57109317;