Genetic Variant ENST00000630920.1:n.1335T>C (chr8-127401733-T-C) – 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.1335T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 152,262 control chromosomes in the GnomAD database, including 152 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 0.024 ( 152 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCAT2
ENST00000630920.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269

Publications

3 publications found

Variant links:

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0816 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCAT2	NR_109834.1	MANE Select	n.1335T>C		non_coding_transcript_exon	Exon 1 of 1
	CASC8	NR_117100.1		n.1176+19096A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CCAT2	ENST00000630920.1	TSL:6 MANE Select	n.1335T>C	non_coding_transcript_exon	Exon 1 of 1
CASC8	ENST00000501396.6	TSL:1	n.546+19096A>G	intron	N/A
CASC8	ENST00000502082.5	TSL:1	n.1176+19096A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3659

AN:

152144

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0842

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0191

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

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)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0240

AC:

3659

AN:

152262

Hom.:

152

Cov.:

AF XY:

0.0226

AC XY:

1681

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0839

AC:

3485

AN:

41524

American (AMR)

AF:

0.00784

AC:

120

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68026

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00771

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

(source)

DANN

Benign

0.77

PhyloP100

-0.27

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