rs2976387

Variant names:

• chr8-142677946-G-A
• rs2976387
• ENST00000505305.1:n.262-3381G>A

Variant summary

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

The ENST00000510969.1(PSCA):​n.249-3381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,994 control chromosomes in the GnomAD database, including 11,513 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 0.37 (11513 hom., cov: 32)
• Consequence: PSCA ENST00000510969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

PSCA (HGNC:9500): (prostate stem cell antigen) This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas. This gene includes a polymorphism that results in an upstream start codon in some individuals; this polymorphism is thought to be associated with a risk for certain gastric and bladder cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2	n.273-3381G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000505305.1	n.262-3381G>A		intron_variant	Intron 1 of 1	3
PSCA	ENST00000510969.1	n.249-3381G>A		intron_variant	Intron 1 of 2	2
JRK	ENST00000587883.5	n.265-1738C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56473 AN: 151876 Hom.: 11498 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.372 AC: 56508 AN: 151994 Hom.: 11513 Cov.: 32 AF XY: 0.374 AC XY: 27759 AN XY: 74312

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.381

Alfa AF: 0.390 Hom.: 1813

Bravo AF: 0.362

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2976387; hg19: chr8-143759364;