8-127467292-T-C

Variant names:

• chr8-127467292-T-C
• rs3999775
• ENST00000502056.1:n.1041+11791A>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+11791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,700 control chromosomes in the GnomAD database, including 48,063 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 0.79 (48063 hom., cov: 33)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 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+11791A>G		intron	N/A
	CASC8	NR_117100.1		n.1041+11791A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1041+11791A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+11791A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.791 AC: 119828 AN: 151582 Hom.: 48065 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.790 AC: 119860 AN: 151700 Hom.: 48063 Cov.: 33 AF XY: 0.787 AC XY: 58375 AN XY: 74128

African (AFR) AF: 0.642 AC: 26536 AN: 41332

American (AMR) AF: 0.828 AC: 12647 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3204 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3796 AN: 5146

South Asian (SAS) AF: 0.826 AC: 3985 AN: 4822

European-Finnish (FIN) AF: 0.774 AC: 8127 AN: 10498

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58722 AN: 67846

Other (OTH) AF: 0.827 AC: 1747 AN: 2112

Alfa AF: 0.821 Hom.: 13840

Bravo AF: 0.785

Asia WGS AF: 0.722 AC: 2510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.64
PhyloP100		-0.17

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: rs3999775;

hg19: chr8-128479537;