8-127473719-A-G

Variant names:

• chr8-127473719-A-G
• rs10109700
• ENST00000502056.1:n.1041+5364T>C

Variant summary

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

The ENST00000502056.1(CASC8):​n.1041+5364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,166 control chromosomes in the GnomAD database, including 53,310 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 0.83 (53310 hom., cov: 31)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 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.1041+5364T>C		intron	N/A
	CASC8	NR_117100.1		n.1041+5364T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1041+5364T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+5364T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126456 AN: 152048 Hom.: 53294 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.831 AC: 126515 AN: 152166 Hom.: 53310 Cov.: 31 AF XY: 0.831 AC XY: 61802 AN XY: 74400

African (AFR) AF: 0.680 AC: 28182 AN: 41468

American (AMR) AF: 0.896 AC: 13702 AN: 15296

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

East Asian (EAS) AF: 0.846 AC: 4365 AN: 5160

South Asian (SAS) AF: 0.871 AC: 4204 AN: 4826

European-Finnish (FIN) AF: 0.825 AC: 8746 AN: 10606

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61138 AN: 68018

Other (OTH) AF: 0.856 AC: 1810 AN: 2114

Alfa AF: 0.872 Hom.: 22285

Bravo AF: 0.827

Asia WGS AF: 0.795 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.36
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs10109700; hg19: chr8-128485964;