8-127294819-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.149-27254C>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 0.0526 in 152,264 control chromosomes in the GnomAD database, including 454 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 0.053 (454 hom., cov: 32)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC21	NR_117099.1	n.149-27254C>T		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-4759G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-4759G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7997 AN: 152146 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0526 AC: 8004 AN: 152264 Hom.: 454 Cov.: 32 AF XY: 0.0565 AC XY: 4209 AN XY: 74468

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0272 Hom.: 117

Bravo AF: 0.0558

Asia WGS AF: 0.192 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	12
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11994592; hg19: chr8-128307064;