rs1930165

Positions:

• chr10-54542170-G-A
• chr10-54542170-G-C
• chr10-54542170-G-T

Variant summary

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

The NM_033056.4(PCDH15):​c.92-14293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,992 control chromosomes in the GnomAD database, including 15,462 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 0.44 (15462 hom., cov: 33)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.92-14293C>T		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.92-14293C>T		intron_variant		ENST00000320301.11	NP_149045.3
LOC105378311	NR_134503.1	n.88-26395G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.92-14293C>T		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.92-14293C>T		intron_variant			NM_001384140.1	ENSP00000495195
	ENST00000422842.1	n.88-26395G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67105 AN: 151874 Hom.: 15460 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.442 AC: 67145 AN: 151992 Hom.: 15462 Cov.: 33 AF XY: 0.443 AC XY: 32934 AN XY: 74288

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.430

Alfa AF: 0.456 Hom.: 21322

Bravo AF: 0.431

Asia WGS AF: 0.614 AC: 2131 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.40

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: rs1930165; hg19: chr10-56301930;