rs2976392

Variant names:

• chr8-142681514-G-A
• rs2976392
• NM_005672.5:c.133+80G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-142681514-G-A
• chr8-142681514-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005672.5(PSCA):​c.133+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,296,764 control chromosomes in the GnomAD database, including 134,274 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 0.45 (15416 hom., cov: 32)
  • Exomes 𝑓: 0.45 (118858 hom.)
• Consequence: PSCA NM_005672.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 82 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NM_005672.5	c.133+80G>A		intron_variant	Intron 2 of 2	ENST00000301258.5	NP_005663.2
PSCA	NR_033343.2	n.380+80G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5	c.133+80G>A		intron_variant	Intron 2 of 2	1	NM_005672.5	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68087 AN: 151782 Hom.: 15383 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.463 AC: 66033 AN: 142688 AF XY: 0.460

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.448

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.450 AC: 514940 AN: 1144862 Hom.: 118858 Cov.: 15 AF XY: 0.450 AC XY: 258545 AN XY: 574178

African (AFR) AF: 0.402 AC: 10748 AN: 26766

American (AMR) AF: 0.554 AC: 19438 AN: 35104

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 11875 AN: 23448

East Asian (EAS) AF: 0.502 AC: 17299 AN: 34466

South Asian (SAS) AF: 0.451 AC: 33307 AN: 73882

European-Finnish (FIN) AF: 0.504 AC: 21325 AN: 42282

Middle Eastern (MID) AF: 0.493 AC: 2573 AN: 5214

European-Non Finnish (NFE) AF: 0.441 AC: 376388 AN: 854120

Other (OTH) AF: 0.443 AC: 21987 AN: 49580

GnomAD4 genome AF: 0.449 AC: 68162 AN: 151902 Hom.: 15416 Cov.: 32 AF XY: 0.450 AC XY: 33385 AN XY: 74242

African (AFR) AF: 0.414 AC: 17121 AN: 41382

American (AMR) AF: 0.514 AC: 7848 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3464

East Asian (EAS) AF: 0.353 AC: 1818 AN: 5154

South Asian (SAS) AF: 0.415 AC: 2000 AN: 4816

European-Finnish (FIN) AF: 0.507 AC: 5366 AN: 10576

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30778 AN: 67930

Other (OTH) AF: 0.449 AC: 946 AN: 2106

Alfa AF: 0.451 Hom.: 17175

Bravo AF: 0.447

Asia WGS AF: 0.406 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2976392; hg19: chr8-143762932; COSMIC: COSV56652755;