Genetic Variant CASC8:n.1042-2186G>A (chr8-127445906-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.1042-2186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,058 control chromosomes in the GnomAD database, including 9,131 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 ( 9131 hom., cov: 32)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

4 publications found

Variant links:

Genes affected

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

CASC8 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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1042-2186G>A		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1042-24943G>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.1042-2186G>A		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1042-24943G>A		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46329

AN:

151940

Hom.:

9104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.296

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

GnomAD4 genome

AF:

0.305

AC:

46399

AN:

152058

Hom.:

9131

Cov.:

AF XY:

0.299

AC XY:

22198

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.561

AC:

23227

AN:

41432

American (AMR)

AF:

0.205

AC:

3138

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1172

AN:

3468

East Asian (EAS)

AF:

0.0505

AC:

262

AN:

5184

South Asian (SAS)

AF:

0.168

AC:

813

AN:

4828

European-Finnish (FIN)

AF:

0.224

AC:

2366

AN:

10552

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14537

AN:

67990

Other (OTH)

AF:

0.293

AC:

620

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1491

2982

4472

5963

7454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.241

Hom.:

20251

Bravo

AF:

0.317

Asia WGS

AF:

0.143

AC:

503

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.2

(source)

DANN

Benign

0.47

PhyloP100

-0.37

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