dbSNP rs7000448: CASC8:n.1042-7962G>A (chr8-127428925-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NR_117100.1(CASC8):n.1042-7962G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NR_117100.1 is not a MANE Select or MANE Plus Clinical transcript for CASC8; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.445 (AC=67,584) in the gnomAD database across 151,824 control chromosomes, including 16,675 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.66. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16675 hom., cov: 31)

Consequence

CASC8
NR_117100.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

60 publications found

Variant links:

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

CASC8 links:

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new If you want to explore the variant's impact on the transcript NR_117100.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6604 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_117100.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1042-7962G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CASC8	ENST00000502082.5	TSL:1	n.1042-7962G>A	intron	N/A
CASC8	ENST00000842817.1		n.82-7962G>A	intron	N/A
CASC8	ENST00000842818.1		n.137+6139G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67517

AN:

151706

Hom.:

16653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.451

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

GnomAD4 genome

AF:

0.445

AC:

67584

AN:

151824

Hom.:

16675

Cov.:

AF XY:

0.441

AC XY:

32681

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.667

AC:

27613

AN:

41398

American (AMR)

AF:

0.319

AC:

4863

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1659

AN:

3468

East Asian (EAS)

AF:

0.296

AC:

1527

AN:

5160

South Asian (SAS)

AF:

0.256

AC:

1232

AN:

4806

European-Finnish (FIN)

AF:

0.435

AC:

4555

AN:

10482

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.363

AC:

24653

AN:

67926

Other (OTH)

AF:

0.446

AC:

941

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1752

3503

5255

7006

8758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.393

Hom.:

35352

Bravo

AF:

0.448

Asia WGS

AF:

0.285

AC:

995

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.241

AC:

29509

AN:

122668

Turkish Variome

AF:

0.403

AC:

622

AN:

1544

Hom.:

126

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.337

AC:

3023

AN:

8960

Hom.:

539

ABraOM SABE-WGS-1171

AF:

0.458

AC:

1073

AN:

2342

Hom.:

243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.22

(source)

DANN

Benign

0.39

PhyloP100

-0.21

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over