Genetic Variant CCAT2:n.662G>T (chr8-127401060-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Publications

803 publications found

Variant links:

COSMIC-nc: COSV72370033

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]

CCAT2 links:

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

CASC8 links:

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]

POU5F1B links:

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]

PCAT1 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000630920.1. 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
	CCAT2	NR_109834.1	MANE Select	n.662G>T		non_coding_transcript_exon	Exon 1 of 1
	CASC8	NR_117100.1		n.1176+19769C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CCAT2	ENST00000630920.1	TSL:6 MANE Select	n.662G>T	non_coding_transcript_exon	Exon 1 of 1
CASC8	ENST00000501396.6	TSL:1	n.546+19769C>A	intron	N/A
CASC8	ENST00000502082.5	TSL:1	n.1176+19769C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58042

AN:

152022

Hom.:

13511

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.382

AC:

58042

AN:

152140

Hom.:

13516

Cov.:

AF XY:

0.386

AC XY:

28736

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1650

3300

4950

6600

8250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

4.4

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over