rs6983267

Variant names:

• chr8-127401060-G-T
• rs6983267
• ENST00000630920.1:n.662G>T

Variant summary

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

The ENST00000630920.1(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 ENST00000630920.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• Publications: 803 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCAT2	NR_109834.1	n.662G>T		non_coding_transcript_exon_variant	Exon 1 of 1	ENST00000630920.1
CASC8	NR_117100.1	n.1176+19769C>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCAT2	ENST00000630920.1	n.662G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6	NR_109834.1

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

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: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.104 AC: 4336 AN: 41526

American (AMR) AF: 0.442 AC: 6761 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1758 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3107 AN: 5166

South Asian (SAS) AF: 0.495 AC: 2391 AN: 4830

European-Finnish (FIN) AF: 0.474 AC: 5006 AN: 10570

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33344 AN: 67974

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.461 Hom.: 81574

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
PhyloP100		4.4

Splicing

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

Other links and lift over

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