Genetic Variant CASC8:n.1042-10849G>A (chr8-127454569-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 ENST00000502056.1(CASC8):n.1042-10849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,108 control chromosomes in the GnomAD database, including 3,830 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 0.21 ( 3830 hom., cov: 33)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

12 publications found

Variant links:

Genes affected

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

CASC8 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1042-10849G>A		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1041+24514G>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1 link	n.1042-10849G>A		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1041+24514G>A		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31763

AN:

151990

Hom.:

3819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.216

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

GnomAD4 genome

AF:

0.209

AC:

31787

AN:

152108

Hom.:

3830

Cov.:

AF XY:

0.216

AC XY:

16037

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.173

AC:

7193

AN:

41492

American (AMR)

AF:

0.327

AC:

4998

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

455

AN:

3472

East Asian (EAS)

AF:

0.520

AC:

2695

AN:

5182

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4820

European-Finnish (FIN)

AF:

0.215

AC:

2275

AN:

10574

Middle Eastern (MID)

AF:

0.193

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.181

AC:

12316

AN:

67972

Other (OTH)

AF:

0.215

AC:

454

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1252

2504

3756

5008

6260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.191

Hom.:

13252

Bravo

AF:

0.215

Asia WGS

AF:

0.345

AC:

1196

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.42

(source)

DANN

Benign

0.61

PhyloP100

-1.5

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