chr8-127400902-C-T

Variant names:

• chr8-127400902-C-T
• rs10808556
• ENST00000630920.1:n.504C>T

Variant summary

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

The ENST00000630920.1(CCAT2):​n.504C>T 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 0.512 in 152,086 control chromosomes in the GnomAD database, including 21,523 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 0.51 (21517 hom., cov: 32)
  • Exomes 𝑓: 0.52 (6 hom.)
• Consequence: CCAT2 ENST00000630920.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 35 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAT2	NR_109834.1	n.504C>T		non_coding_transcript_exon_variant	Exon 1 of 1	ENST00000630920.1
CASC8	NR_117100.1	n.1176+19927G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCAT2	ENST00000630920.1	n.504C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6	NR_109834.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77806 AN: 151920 Hom.: 21511 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.522 AC: 24 AN: 46 Hom.: 6 Cov.: 0 AF XY: 0.528 AC XY: 19 AN XY: 36

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

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: 0.553 AC: 21 AN: 38

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.512 AC: 77833 AN: 152040 Hom.: 21517 Cov.: 32 AF XY: 0.517 AC XY: 38449 AN XY: 74322

African (AFR) AF: 0.289 AC: 11987 AN: 41478

American (AMR) AF: 0.643 AC: 9836 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3470

East Asian (EAS) AF: 0.644 AC: 3320 AN: 5158

South Asian (SAS) AF: 0.600 AC: 2887 AN: 4814

European-Finnish (FIN) AF: 0.572 AC: 6027 AN: 10544

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39964 AN: 67972

Other (OTH) AF: 0.564 AC: 1192 AN: 2114

Alfa AF: 0.573 Hom.: 49002

Bravo AF: 0.508

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs10808556; hg19: chr8-128413147;