rs378854

chr8-127311574-C-T

Variant summary

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

The NR_117099.1(CASC21):n.149-10499C>T variant causes a intron, non coding transcript 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: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953

Genes affected

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

CASC21 (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]

ACMG classification

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/exons	MANE	UniProt
CASC21	NR_117099.1	n.149-10499C>T		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-21514G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-21514G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47031 AN: 151806 Hom.: 7704 Cov.: 32

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: 39 AN: 264 Hom.: 7 Cov.: 0 AF XY: 0.170 AC XY: 30 AN XY: 176

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.: 32 AF XY: 0.310 AC XY: 23052 AN XY: 74280

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

Other links and lift over

dbSNP: rs378854; hg19: chr8-128323819;