Genetic Variant ENST00000501396.6:n.546+36562C>T (chr8-127384267-G-A) – 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.546+36562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,136 control chromosomes in the GnomAD database, including 58,422 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 0.87 ( 58422 hom., cov: 30)

Consequence

CASC8
ENST00000501396.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00300

Publications

8 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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1 link	n.458-8237G>A		intron_variant	Intron 3 of 3
CASC8	NR_117100.1 link	n.1176+36562C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC8	ENST00000501396.6 link	n.546+36562C>T	intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5 link	n.1176+36562C>T	intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2 link	n.290-8237G>A	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

132914

AN:

152018

Hom.:

58385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.958

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.953

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.909

Gnomad OTH

AF:

0.883

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

GnomAD4 genome

AF:

0.874

AC:

133008

AN:

152136

Hom.:

58422

Cov.:

AF XY:

0.876

AC XY:

65145

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.804

AC:

33328

AN:

41462

American (AMR)

AF:

0.845

AC:

12911

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

3323

AN:

3470

East Asian (EAS)

AF:

0.859

AC:

4430

AN:

5160

South Asian (SAS)

AF:

0.849

AC:

4101

AN:

4828

European-Finnish (FIN)

AF:

0.953

AC:

10111

AN:

10608

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.909

AC:

61814

AN:

68010

Other (OTH)

AF:

0.885

AC:

1872

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

833

1665

2498

3330

4163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.898

Hom.:

77298

Bravo

AF:

0.859

Asia WGS

AF:

0.851

AC:

2961

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.0

(source)

DANN

Benign

0.66

PhyloP100

0.0030

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