rs1930175

Positions:

• chr10-54566589-C-A
• chr10-54566589-C-G
• chr10-54566589-C-T

Variant summary

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

The NM_033056.4(PCDH15):​c.92-38712G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,174 control chromosomes in the GnomAD database, including 66,991 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 (66991 hom., cov: 32)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.92-38712G>T		intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.92-38712G>T		intron_variant		ENST00000320301.11
LOC105378311	NR_134503.1	n.88-1976C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.92-38712G>T		intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.92-38712G>T		intron_variant			NM_001384140.1
	ENST00000422842.1	n.88-1976C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142263 AN: 152056 Hom.: 66952 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.935 AC: 142357 AN: 152174 Hom.: 66991 Cov.: 32 AF XY: 0.938 AC XY: 69786 AN XY: 74396

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.986

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.982

Gnomad4 OTH AF: 0.952

Alfa AF: 0.973 Hom.: 28159

Bravo AF: 0.930

Asia WGS AF: 0.919 AC: 3195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.29

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: rs1930175; hg19: chr10-56326349;