Genetic Variant CASC8:n.1042-20720A>G (chr8-127441683-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 ENST00000502082.5(CASC8):n.1042-20720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,108 control chromosomes in the GnomAD database, including 9,997 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 0.36 ( 9997 hom., cov: 32)

Consequence

CASC8
ENST00000502082.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.510

Publications

10 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1 link	n.1042-20720A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5 link	n.1042-20720A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54419

AN:

151990

Hom.:

9991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.392

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

GnomAD4 genome

AF:

0.358

AC:

54442

AN:

152108

Hom.:

9997

Cov.:

AF XY:

0.357

AC XY:

26546

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.349

AC:

14473

AN:

41478

American (AMR)

AF:

0.286

AC:

4376

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1689

AN:

3472

East Asian (EAS)

AF:

0.296

AC:

1530

AN:

5168

South Asian (SAS)

AF:

0.272

AC:

1310

AN:

4822

European-Finnish (FIN)

AF:

0.426

AC:

4512

AN:

10582

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25200

AN:

67980

Other (OTH)

AF:

0.387

AC:

818

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1804

3608

5411

7215

9019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.366

Hom.:

43970

Bravo

AF:

0.350

Asia WGS

AF:

0.275

AC:

960

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.2

(source)

DANN

Benign

0.57

PhyloP100

-0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-127441683-T-C

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