Genetic Variant CASC8:n.686+11441G>A (chr8-127311574-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.686+11441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,188 control chromosomes in the GnomAD database, including 7,716 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 ( 7709 hom., cov: 32)

Exomes 𝑓: 0.15 ( 7 hom. )

Consequence

CASC8
ENST00000501396.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

Publications

30 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:

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

CASC21 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.149-10499C>T		intron	N/A
	CASC8	NR_117100.1		n.1177-21514G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CASC8	ENST00000501396.6	TSL:1	n.686+11441G>A	intron	N/A
CASC8	ENST00000502082.5	TSL:1	n.1177-21514G>A	intron	N/A
CASC8	ENST00000523825.3	TSL:1	n.547-21514G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47031

AN:

151806

Hom.:

7704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.148

AC:

AN:

264

Hom.:

Cov.:

AF XY:

0.170

AC XY:

AN XY:

176

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.0758

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.185

AC:

AN:

162

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

47061

AN:

151924

Hom.:

7709

Cov.:

AF XY:

0.310

AC XY:

23052

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.201

AC:

8308

AN:

41390

American (AMR)

AF:

0.319

AC:

4873

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1185

AN:

3466

East Asian (EAS)

AF:

0.367

AC:

1895

AN:

5170

South Asian (SAS)

AF:

0.477

AC:

2294

AN:

4810

European-Finnish (FIN)

AF:

0.293

AC:

3085

AN:

10542

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24083

AN:

67956

Other (OTH)

AF:

0.329

AC:

694

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1636

3272

4907

6543

8179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.347

Hom.:

4091

Bravo

AF:

0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.0

(source)

DANN

Benign

0.51

PhyloP100

0.95

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over