dbSNP rs378854: CASC8:n.686+11441G>A (chr8-127311574-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000642795.1(PCAT1):n.319C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,188 control chromosomes in the GnomAD database, including 7,716 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 0.31 ( 7709 hom., cov: 32)

Exomes 𝑓: 0.15 ( 7 hom. )

Consequence

PCAT1
ENST00000642795.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

Variant links:

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

CASC8 links:

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

PCAT1 links:

CASC21 (HGNC:49836): (cancer susceptibility 21)

CASC21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1 link	n.149-10499C>T		intron_variant	Intron 1 of 3
CASC8	NR_117100.1 link	n.1177-21514G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.5 link	n.686+11441G>A	intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5 link	n.1177-21514G>A	intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.2 link	n.547-21514G>A	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47031

AN:

151806

Hom.:

7704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.148

AC:

AN:

264

Hom.:

Cov.:

AF XY:

0.170

AC XY:

AN XY:

176

show subpopulations

Gnomad4 ASJ exome

AF:

0.0625

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.0758

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.310

AC:

47061

AN:

151924

Hom.:

7709

Cov.:

AF XY:

0.310

AC XY:

23052

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.342

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.477

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.342

Hom.:

2209

Bravo

AF:

0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.0

DANN

Benign

0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over