dbSNP rs10956364: CASC8:n.547-43483G>A (chr8-127366637-C-T) – 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.547-43483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,972 control chromosomes in the GnomAD database, including 20,442 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 ( 20442 hom., cov: 32)

Consequence

CASC8
ENST00000501396.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

Publications

10 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1 link	n.458-25867C>T		intron_variant	Intron 3 of 3
CASC8	NR_117100.1 link	n.1176+54192G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.6 link	n.547-43483G>A	intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5 link	n.1176+54192G>A	intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2 link	n.290-25867C>T	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78212

AN:

151854

Hom.:

20443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.486

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

GnomAD4 genome

AF:

0.515

AC:

78219

AN:

151972

Hom.:

20442

Cov.:

AF XY:

0.516

AC XY:

38308

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.462

AC:

19130

AN:

41416

American (AMR)

AF:

0.441

AC:

6731

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1911

AN:

3470

East Asian (EAS)

AF:

0.466

AC:

2407

AN:

5168

South Asian (SAS)

AF:

0.476

AC:

2293

AN:

4820

European-Finnish (FIN)

AF:

0.617

AC:

6519

AN:

10560

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37699

AN:

67954

Other (OTH)

AF:

0.482

AC:

1017

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1941

3882

5822

7763

9704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.533

Hom.:

15491

Bravo

AF:

0.498

Asia WGS

AF:

0.447

AC:

1556

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.6

(source)

DANN

Benign

0.62

PhyloP100

0.68

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