rs2976391

Variant names:

• chr8-142681306-C-A
• rs2976391
• NM_005672.5:c.26-21C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-142681306-C-A
• chr8-142681306-C-G
• chr8-142681306-C-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.26-21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,538,732 control chromosomes in the GnomAD database, including 164,741 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 (14552 hom., cov: 32)
  • Exomes 𝑓: 0.46 (150189 hom.)
• Consequence: PSCA NM_005672.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 19 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	NM_005672.5	MANE Select	c.26-21C>A		intron	N/A	NP_005663.2	O43653
	PSCA	NR_033343.2		n.273-21C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	ENST00000301258.5	TSL:1 MANE Select	c.26-21C>A		intron	N/A	ENSP00000301258.4	O43653
	PSCA	ENST00000918921.1		c.26-21C>A		intron	N/A	ENSP00000588980.1
	PSCA	ENST00000966863.1		c.26-21C>A		intron	N/A	ENSP00000636922.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66232 AN: 151700 Hom.: 14548 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.445

GnomAD2 exomes AF: 0.423 AC: 65044 AN: 153664 AF XY: 0.425

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.462 AC: 640295 AN: 1386912 Hom.: 150189 Cov.: 27 AF XY: 0.459 AC XY: 314253 AN XY: 684370

African (AFR) AF: 0.403 AC: 12645 AN: 31366

American (AMR) AF: 0.375 AC: 13373 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 10769 AN: 24978

East Asian (EAS) AF: 0.254 AC: 9043 AN: 35670

South Asian (SAS) AF: 0.372 AC: 29339 AN: 78886

European-Finnish (FIN) AF: 0.440 AC: 21378 AN: 48632

Middle Eastern (MID) AF: 0.449 AC: 2398 AN: 5340

European-Non Finnish (NFE) AF: 0.482 AC: 515493 AN: 1068876

Other (OTH) AF: 0.450 AC: 25857 AN: 57498

GnomAD4 genome AF: 0.436 AC: 66244 AN: 151820 Hom.: 14552 Cov.: 32 AF XY: 0.434 AC XY: 32219 AN XY: 74198

African (AFR) AF: 0.399 AC: 16532 AN: 41394

American (AMR) AF: 0.415 AC: 6347 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3464

East Asian (EAS) AF: 0.321 AC: 1651 AN: 5146

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4645 AN: 10546

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32220 AN: 67862

Other (OTH) AF: 0.438 AC: 926 AN: 2114

Alfa AF: 0.454 Hom.: 9526

Bravo AF: 0.433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.84
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: rs2976391; hg19: chr8-143762724; COSMIC: COSV56652616;