dbSNP rs13262406: CASC8:n.547-18340T>C (chr8-127341494-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000501396.6(CASC8):n.547-18340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,002 control chromosomes in the GnomAD database, including 7,899 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 0.31 ( 7899 hom., cov: 32)

Consequence

CASC8
ENST00000501396.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

Publications

3 publications found

Variant links:

Genes affected

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

CASC8 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:

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:

CASC21 (HGNC:49836): (cancer susceptibility 21)

CASC21 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1 link	n.457+2059A>G		intron_variant	Intron 3 of 3
CASC8	NR_117100.1 link	n.1177-51434T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.6 link	n.547-18340T>C	intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5 link	n.1177-51434T>C	intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2 link	n.289+2059A>G	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47695

AN:

151884

Hom.:

7885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.314

AC:

47763

AN:

152002

Hom.:

7899

Cov.:

AF XY:

0.309

AC XY:

22983

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.295

AC:

12254

AN:

41470

American (AMR)

AF:

0.445

AC:

6799

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1206

AN:

3466

East Asian (EAS)

AF:

0.179

AC:

924

AN:

5154

South Asian (SAS)

AF:

0.357

AC:

1720

AN:

4814

European-Finnish (FIN)

AF:

0.200

AC:

2117

AN:

10576

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21437

AN:

67936

Other (OTH)

AF:

0.357

AC:

753

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1658

3315

4973

6630

8288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.312

Hom.:

3249

Bravo

AF:

0.331

Asia WGS

AF:

0.291

AC:

1009

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

(source)

DANN

Benign

0.72

PhyloP100

-0.057

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over