8-127482236-C-G

Variant names:

• chr8-127482236-C-G
• rs9643226
• ENST00000502056.1:n.-97G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502056.1(CASC8):​n.-97G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,228 control chromosomes in the GnomAD database, including 60,819 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 0.89 (60800 hom., cov: 30)
  • Exomes 𝑓: 0.90 (19 hom.)
• Consequence: CASC8 ENST00000502056.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 11 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502056.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.-97G>C		upstream_gene	N/A
	CASC8	NR_117100.1		n.-97G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.-97G>C		upstream_gene	N/A
	CASC8	ENST00000502082.5	TSL:1	n.-97G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135836 AN: 152062 Hom.: 60751 Cov.: 30

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.905

GnomAD4 exome AF: 0.896 AC: 43 AN: 48 Hom.: 19 AF XY: 0.917 AC XY: 33 AN XY: 36

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.861 AC: 31 AN: 36

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.893 AC: 135941 AN: 152180 Hom.: 60800 Cov.: 30 AF XY: 0.890 AC XY: 66252 AN XY: 74418

African (AFR) AF: 0.893 AC: 37061 AN: 41496

American (AMR) AF: 0.924 AC: 14119 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3265 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4341 AN: 5170

South Asian (SAS) AF: 0.873 AC: 4215 AN: 4830

European-Finnish (FIN) AF: 0.825 AC: 8740 AN: 10600

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61197 AN: 68014

Other (OTH) AF: 0.900 AC: 1894 AN: 2104

Alfa AF: 0.835 Hom.: 1805

Bravo AF: 0.898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.38
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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.

Other links and lift over

dbSNP: rs9643226;

hg19: chr8-128494481;