rs924993

Variant names:

• chr8-127292254-G-A
• rs924993
• ENST00000501396.5:n.687-2194C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000605028.1(ENSG00000271509):​n.22G>A 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 0.0507 in 152,166 control chromosomes in the GnomAD database, including 447 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 0.051 (447 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ENSG00000271509 ENST00000605028.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

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

ENSG00000271509 (HGNC:):

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-29819G>A		intron_variant	Intron 1 of 3
CASC8	NR_117100.1	n.1177-2194C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.687-2194C>T		intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5	n.1177-2194C>T		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.2	n.547-2194C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7692 AN: 152042 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0507 AC: 7712 AN: 152160 Hom.: 447 Cov.: 32 AF XY: 0.0561 AC XY: 4173 AN XY: 74378

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0288 Hom.: 186

Bravo AF: 0.0608

Asia WGS AF: 0.204 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs924993; hg19: chr8-128304499;