Genetic Variant CASC8:n.1041+11791A>G (chr8-127467292-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.1041+11791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,700 control chromosomes in the GnomAD database, including 48,063 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 0.79 ( 48063 hom., cov: 33)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1041+11791A>G		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1041+11791A>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.1041+11791A>G		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1041+11791A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

119828

AN:

151582

Hom.:

48065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.903

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.923

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.833

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

GnomAD4 genome

AF:

0.790

AC:

119860

AN:

151700

Hom.:

48063

Cov.:

AF XY:

0.787

AC XY:

58375

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.642

AC:

26536

AN:

41332

American (AMR)

AF:

0.828

AC:

12647

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.923

AC:

3204

AN:

3470

East Asian (EAS)

AF:

0.738

AC:

3796

AN:

5146

South Asian (SAS)

AF:

0.826

AC:

3985

AN:

4822

European-Finnish (FIN)

AF:

0.774

AC:

8127

AN:

10498

Middle Eastern (MID)

AF:

0.946

AC:

278

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58722

AN:

67846

Other (OTH)

AF:

0.827

AC:

1747

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1250

2500

3750

5000

6250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.821

Hom.:

13840

Bravo

AF:

0.785

Asia WGS

AF:

0.722

AC:

2510

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.2

(source)

DANN

Benign

0.64

PhyloP100

-0.17

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