Genetic Variant CASC8:n.1042-16677A>G (chr8-127460397-T-C) – 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.1042-16677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 151,970 control chromosomes in the GnomAD database, including 53,437 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 0.83 ( 53437 hom., cov: 30)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.871

Publications

6 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=-1.03).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1042-16677A>G		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1041+18686A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1 link	n.1042-16677A>G		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1041+18686A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126494

AN:

151852

Hom.:

53407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.903

Gnomad AMR

AF:

0.894

Gnomad ASJ

AF:

0.942

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.946

Gnomad NFE

AF:

0.900

Gnomad OTH

AF:

0.860

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

GnomAD4 genome

AF:

0.833

AC:

126576

AN:

151970

Hom.:

53437

Cov.:

AF XY:

0.833

AC XY:

61838

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.679

AC:

28094

AN:

41354

American (AMR)

AF:

0.894

AC:

13664

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

3269

AN:

3472

East Asian (EAS)

AF:

0.860

AC:

4457

AN:

5180

South Asian (SAS)

AF:

0.873

AC:

4200

AN:

4812

European-Finnish (FIN)

AF:

0.829

AC:

8728

AN:

10526

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.900

AC:

61260

AN:

68030

Other (OTH)

AF:

0.854

AC:

1801

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

988

1975

2963

3950

4938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.876

Hom.:

26176

Bravo

AF:

0.829

Asia WGS

AF:

0.809

AC:

2813

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

0.81

(source)

DANN

Benign

0.61

PhyloP100

-0.87

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