10-54571774-A-T

Variant summary

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

The NM_033056.4(PCDH15):c.92-43897T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,228 control chromosomes in the GnomAD database, including 67,026 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 0.94 (67026 hom., cov: 32)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.92-43897T>A		intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.92-43897T>A		intron_variant		ENST00000320301.11
LOC105378311	NR_134503.1	n.198+3099A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.92-43897T>A		intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.92-43897T>A		intron_variant			NM_001384140.1
	ENST00000422842.1	n.198+3099A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142467 AN: 152112 Hom.: 66985 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.937 AC: 142562 AN: 152228 Hom.: 67026 Cov.: 32 AF XY: 0.936 AC XY: 69671 AN XY: 74426

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.945

Alfa AF: 0.964 Hom.: 3346

Bravo AF: 0.927

Asia WGS AF: 0.905 AC: 3145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.35

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: rs1930152; hg19: chr10-56331534;