8-127476954-T-C

Variant names:

• chr8-127476954-T-C
• rs7826179
• ENST00000502056.1:n.1041+2129A>G

Variant summary

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

The ENST00000502056.1(CASC8):​n.1041+2129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 151,616 control chromosomes in the GnomAD database, including 64,326 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 0.92 (64326 hom., cov: 26)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.1041+2129A>G		intron	N/A
	CASC8	NR_117100.1		n.1041+2129A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1041+2129A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+2129A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139416 AN: 151502 Hom.: 64273 Cov.: 26

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.920 AC: 139525 AN: 151616 Hom.: 64326 Cov.: 26 AF XY: 0.917 AC XY: 67859 AN XY: 74008

African (AFR) AF: 0.984 AC: 40693 AN: 41372

American (AMR) AF: 0.931 AC: 14196 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3263 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4358 AN: 5134

South Asian (SAS) AF: 0.874 AC: 4167 AN: 4766

European-Finnish (FIN) AF: 0.831 AC: 8644 AN: 10398

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61151 AN: 67916

Other (OTH) AF: 0.920 AC: 1942 AN: 2110

Alfa AF: 0.903 Hom.: 7245

Bravo AF: 0.929

Asia WGS AF: 0.824 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs7826179; hg19: chr8-128489199;