Genetic Variant CASC8:n.546+29560A>C (chr8-127391269-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000501396.6(CASC8):n.546+29560A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,206 control chromosomes in the GnomAD database, including 563 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 0.079 ( 563 hom., cov: 32)

Consequence

CASC8
ENST00000501396.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

4 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1 link	n.458-1235T>G		intron_variant	Intron 3 of 3
CASC8	NR_117100.1 link	n.1176+29560A>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.6 link	n.546+29560A>C	intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5 link	n.1176+29560A>C	intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2 link	n.290-1235T>G	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.0792

AC:

12041

AN:

152088

Hom.:

560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0831

Gnomad EAS

AF:

0.0695

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0892

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0621

Gnomad OTH

AF:

0.0770

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

GnomAD4 genome

AF:

0.0792

AC:

12060

AN:

152206

Hom.:

563

Cov.:

AF XY:

0.0802

AC XY:

5970

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.114

AC:

4725

AN:

41514

American (AMR)

AF:

0.0452

AC:

692

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

288

AN:

3464

East Asian (EAS)

AF:

0.0696

AC:

360

AN:

5170

South Asian (SAS)

AF:

0.112

AC:

541

AN:

4816

European-Finnish (FIN)

AF:

0.0892

AC:

947

AN:

10612

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0621

AC:

4222

AN:

68006

Other (OTH)

AF:

0.0781

AC:

165

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

566

1131

1697

2262

2828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0631

Hom.:

713

Bravo

AF:

0.0753

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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