rs1045531

Variant names:

• chr8-142682129-C-A
• rs1045531
• NM_005672.5:c.342C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-142682129-C-A
• chr8-142682129-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005672.5(PSCA):​c.342C>A​(p.Leu114Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,597,802 control chromosomes in the GnomAD database, including 163,485 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 (14987 hom., cov: 34)
  • Exomes 𝑓: 0.45 (148498 hom.)
• Consequence: PSCA NM_005672.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NM_005672.5	c.342C>A	p.Leu114Leu	synonymous_variant	Exon 3 of 3	ENST00000301258.5	NP_005663.2
PSCA	NR_033343.2	n.589C>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5	c.342C>A	p.Leu114Leu	synonymous_variant	Exon 3 of 3	1	NM_005672.5	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67115 AN: 151980 Hom.: 14960 Cov.: 34

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.454 AC: 103821 AN: 228692 AF XY: 0.452

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.505

Gnomad EAS exome AF: 0.312

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.451 AC: 651339 AN: 1445702 Hom.: 148498 Cov.: 60 AF XY: 0.451 AC XY: 324320 AN XY: 719518

African (AFR) AF: 0.379 AC: 12688 AN: 33436

American (AMR) AF: 0.558 AC: 24772 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 13147 AN: 25986

East Asian (EAS) AF: 0.486 AC: 19241 AN: 39626

South Asian (SAS) AF: 0.450 AC: 38551 AN: 85724

European-Finnish (FIN) AF: 0.501 AC: 20330 AN: 40616

Middle Eastern (MID) AF: 0.490 AC: 2823 AN: 5760

European-Non Finnish (NFE) AF: 0.444 AC: 493203 AN: 1110136

Other (OTH) AF: 0.443 AC: 26584 AN: 60062

GnomAD4 genome AF: 0.442 AC: 67181 AN: 152100 Hom.: 14987 Cov.: 34 AF XY: 0.442 AC XY: 32897 AN XY: 74360

African (AFR) AF: 0.389 AC: 16145 AN: 41504

American (AMR) AF: 0.511 AC: 7816 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1817 AN: 5158

South Asian (SAS) AF: 0.415 AC: 2004 AN: 4824

European-Finnish (FIN) AF: 0.508 AC: 5383 AN: 10606

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30792 AN: 67936

Other (OTH) AF: 0.444 AC: 936 AN: 2108

Alfa AF: 0.450 Hom.: 9348

Bravo AF: 0.439

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.38
DANN	Benign	0.74
PhyloP100		-1.2
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: rs1045531; hg19: chr8-143763547; COSMIC: COSV56652582; COSMIC: COSV56652582;