dbSNP rs1447293: CASC8:n.1042-16355G>A (chr8-127460075-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.1042-16355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,014 control chromosomes in the GnomAD database, including 21,019 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 0.49 ( 21019 hom., cov: 32)

Consequence

CASC8
ENST00000502056.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.388

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1 link	n.1042-16355G>A		intron_variant	Intron 4 of 4
CASC8	NR_117100.1 link	n.1041+19008G>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.1042-16355G>A		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5 link	n.1041+19008G>A		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73976

AN:

151896

Hom.:

21020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.532

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

GnomAD4 genome

AF:

0.487

AC:

73977

AN:

152014

Hom.:

21019

Cov.:

AF XY:

0.489

AC XY:

36310

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.175

AC:

7260

AN:

41466

American (AMR)

AF:

0.558

AC:

8519

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1929

AN:

3470

East Asian (EAS)

AF:

0.485

AC:

2507

AN:

5172

South Asian (SAS)

AF:

0.618

AC:

2982

AN:

4822

European-Finnish (FIN)

AF:

0.571

AC:

6021

AN:

10538

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.630

AC:

42787

AN:

67964

Other (OTH)

AF:

0.529

AC:

1118

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1648

3297

4945

6594

8242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.587

Hom.:

47059

Bravo

AF:

0.470

Asia WGS

AF:

0.477

AC:

1662

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.48

PhyloP100

-0.39

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