8-142682583-G-A

Variant names:

• chr8-142682583-G-A
• rs2976396
• NM_005672.5:c.*451G>A

Variant summary

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

The NM_005672.5(PSCA):​c.*451G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 375,438 control chromosomes in the GnomAD database, including 38,492 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 (14965 hom., cov: 33)
  • Exomes 𝑓: 0.45 (23527 hom.)
• Consequence: PSCA NM_005672.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 24 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005672.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	NM_005672.5	MANE Select	c.*451G>A		3_prime_UTR	Exon 3 of 3	NP_005663.2
	PSCA	NR_033343.2		n.1043G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	ENST00000301258.5	TSL:1 MANE Select	c.*451G>A		3_prime_UTR	Exon 3 of 3	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67059 AN: 151936 Hom.: 14938 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.447 AC: 30789 AN: 68864 AF XY: 0.445

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.312

Gnomad FIN exome AF: 0.503

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.454 AC: 101512 AN: 223382 Hom.: 23527 Cov.: 0 AF XY: 0.454 AC XY: 55263 AN XY: 121856

African (AFR) AF: 0.381 AC: 2425 AN: 6368

American (AMR) AF: 0.546 AC: 8440 AN: 15468

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 2766 AN: 5448

East Asian (EAS) AF: 0.335 AC: 2881 AN: 8606

South Asian (SAS) AF: 0.451 AC: 20934 AN: 46430

European-Finnish (FIN) AF: 0.499 AC: 4725 AN: 9464

Middle Eastern (MID) AF: 0.500 AC: 1178 AN: 2356

European-Non Finnish (NFE) AF: 0.449 AC: 53207 AN: 118372

Other (OTH) AF: 0.456 AC: 4956 AN: 10870

GnomAD4 genome AF: 0.441 AC: 67125 AN: 152056 Hom.: 14965 Cov.: 33 AF XY: 0.442 AC XY: 32854 AN XY: 74326

African (AFR) AF: 0.388 AC: 16110 AN: 41488

American (AMR) AF: 0.511 AC: 7813 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1815 AN: 5162

South Asian (SAS) AF: 0.415 AC: 1995 AN: 4806

European-Finnish (FIN) AF: 0.507 AC: 5368 AN: 10584

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30801 AN: 67948

Other (OTH) AF: 0.444 AC: 935 AN: 2108

Alfa AF: 0.451 Hom.: 17181

Bravo AF: 0.438

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.41
PhyloP100		-0.097
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: rs2976396; hg19: chr8-143764001;