chr8-142680513-C-T

Variant names:

• chr8-142680513-C-T
• rs2294008
• NM_005672.5:c.-26C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005672.5(PSCA):​c.-26C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,552,278 control chromosomes in the GnomAD database, including 159,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15469 hom., cov: 34)
  • Exomes 𝑓: 0.45 (144283 hom.)
• Consequence: PSCA NM_005672.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.133

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.091).
• BP6: Variant 8-142680513-C-T is Benign according to our data. Variant chr8-142680513-C-T is described in ClinVar as [Benign]. Clinvar id is 704509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.-26C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000301258.5	NP_005663.2
PSCA	NM_005672.5	c.-26C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000301258.5	NP_005663.2
PSCA	NR_033343.2	n.273-814C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258	c.-26C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_005672.5	ENSP00000301258.4
PSCA	ENST00000301258	c.-26C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_005672.5	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68242 AN: 152088 Hom.: 15436 Cov.: 34

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.461 AC: 72528 AN: 157352 AF XY: 0.458

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.509

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.451 AC: 631779 AN: 1400072 Hom.: 144283 Cov.: 45 AF XY: 0.452 AC XY: 311864 AN XY: 690692

Gnomad4 AFR exome AF: 0.402 AC: 12715 AN: 31662

Gnomad4 AMR exome AF: 0.553 AC: 19805 AN: 35840

Gnomad4 ASJ exome AF: 0.506 AC: 12755 AN: 25186

Gnomad4 EAS exome AF: 0.496 AC: 17818 AN: 35900

Gnomad4 SAS exome AF: 0.452 AC: 35806 AN: 79254

Gnomad4 FIN exome AF: 0.505 AC: 24960 AN: 49416

Gnomad4 NFE exome AF: 0.444 AC: 479440 AN: 1079230

Gnomad4 Remaining exome AF: 0.444 AC: 25802 AN: 58070

GnomAD4 genome AF: 0.449 AC: 68317 AN: 152206 Hom.: 15469 Cov.: 34 AF XY: 0.450 AC XY: 33458 AN XY: 74420

Gnomad4 AFR AF: 0.414 AC: 0.413791 AN: 0.413791

Gnomad4 AMR AF: 0.514 AC: 0.513595 AN: 0.513595

Gnomad4 ASJ AF: 0.517 AC: 0.516715 AN: 0.516715

Gnomad4 EAS AF: 0.352 AC: 0.352246 AN: 0.352246

Gnomad4 SAS AF: 0.416 AC: 0.415803 AN: 0.415803

Gnomad4 FIN AF: 0.507 AC: 0.507168 AN: 0.507168

Gnomad4 NFE AF: 0.454 AC: 0.453517 AN: 0.453517

Gnomad4 OTH AF: 0.449 AC: 0.448864 AN: 0.448864

Alfa AF: 0.452 Hom.: 74094

Bravo AF: 0.447

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.76
Mutation Taster		=299/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs2294008; hg19: chr8-143761931; COSMIC: COSV56652380;