Genetic Variant CASC8:n.1041+6995A>G (chr8-127472088-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+6995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,212 control chromosomes in the GnomAD database, including 55,136 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 0.85 ( 55136 hom., cov: 32)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.315

Publications

6 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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1041+6995A>G		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1041+6995A>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+6995A>G		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1041+6995A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128972

AN:

152094

Hom.:

55123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.904

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.940

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.876

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

GnomAD4 genome

AF:

0.848

AC:

129029

AN:

152212

Hom.:

55136

Cov.:

AF XY:

0.847

AC XY:

62999

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.733

AC:

30441

AN:

41502

American (AMR)

AF:

0.906

AC:

13863

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.940

AC:

3265

AN:

3472

East Asian (EAS)

AF:

0.851

AC:

4413

AN:

5188

South Asian (SAS)

AF:

0.872

AC:

4207

AN:

4824

European-Finnish (FIN)

AF:

0.825

AC:

8730

AN:

10584

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61169

AN:

68026

Other (OTH)

AF:

0.871

AC:

1837

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

976

1952

2929

3905

4881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.884

Hom.:

28415

Bravo

AF:

0.846

Asia WGS

AF:

0.803

AC:

2794

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.5

(source)

DANN

Benign

0.49

PhyloP100

-0.32

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