rs924993

Variant names:

• chr8-127292254-G-A
• rs924993
• ENST00000501396.6:n.687-2194C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000501396.6(CASC8):​n.687-2194C>T variant causes a intron 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: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.149-29819G>A		intron	N/A
	CASC8	NR_117100.1		n.1177-2194C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.687-2194C>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-2194C>T		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-2194C>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0547 AC: 2270 AN: 41498

American (AMR) AF: 0.118 AC: 1798 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1466 AN: 5178

South Asian (SAS) AF: 0.0969 AC: 466 AN: 4810

European-Finnish (FIN) AF: 0.0440 AC: 466 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0136 AC: 927 AN: 68010

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0309 Hom.: 674

Bravo AF: 0.0608

Asia WGS AF: 0.204 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.0070

Splicing

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

Other links and lift over

dbSNP: rs924993; hg19: chr8-128304499;