rs6983267

Positions:

• chr8-127401060-G-T

Variant summary

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

The NR_109834.1(CCAT2):​n.662G>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.382 in 152,144 control chromosomes in the GnomAD database, including 13,516 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 0.38 (13516 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: CCAT2 NR_109834.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

Genes affected

CCAT2 (HGNC:47044): (colon cancer associated transcript 2) This gene produces a long non-coding RNA that is upregulated in colon cancer and other cancers. This transcript promotes cell proliferation and suppresses apoptosis. It negatively regulates the biogenesis of microRNA 145. [provided by RefSeq, Dec 2017]

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

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCAT2	NR_109834.1	n.662G>T		non_coding_transcript_exon_variant	1/1
CASC8	NR_117100.1	n.1176+19769C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCAT2	ENST00000630920.1	n.662G>T		non_coding_transcript_exon_variant	1/1
CASC8	ENST00000502082.5	n.1176+19769C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58042 AN: 152022 Hom.: 13511 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.382 AC: 58042 AN: 152140 Hom.: 13516 Cov.: 33 AF XY: 0.386 AC XY: 28736 AN XY: 74376

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.423

Alfa AF: 0.475 Hom.: 40970

Bravo AF: 0.364

Asia WGS AF: 0.503 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6983267; hg19: chr8-128413305; COSMIC: COSV72370033; COSMIC: COSV72370033;