dbSNP rs6983267: CASC8:n.546+19769C>A (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 ENST00000645438.1(POU5F1B):c.-559-13828G>T variant causes a intron 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

POU5F1B
ENST00000645438.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Variant links:

Genes affected

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:

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:

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAT2	NR_109834.1 link	n.662G>T		non_coding_transcript_exon_variant	Exon 1 of 1
CASC8	NR_117100.1 link	n.1176+19769C>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.5 link	n.546+19769C>A	intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5 link	n.1176+19769C>A	intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.2 link	n.546+19769C>A	intron_variant	Intron 1 of 1	1

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

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AF:

0.500

AC:

AN:

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

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

Gnomad4 AFR

AF:

0.104

AC:

0.104417

AN:

0.104417

Gnomad4 AMR

AF:

0.442

AC:

0.442242

AN:

0.442242

Gnomad4 ASJ

AF:

0.506

AC:

0.506336

AN:

0.506336

Gnomad4 EAS

AF:

0.601

AC:

0.601432

AN:

0.601432

Gnomad4 SAS

AF:

0.495

AC:

0.495031

AN:

0.495031

Gnomad4 FIN

AF:

0.474

AC:

0.473605

AN:

0.473605

Gnomad4 NFE

AF:

0.491

AC:

0.490541

AN:

0.490541

Gnomad4 OTH

AF:

0.423

AC:

0.423223

AN:

0.423223

Heterozygous variant carriers

1650

3300

4950

6600

8250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.86

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over