chr8-127460075-C-T

Variant names:

• chr8-127460075-C-T
• rs1447293
• ENST00000502056.1:n.1042-16355G>A

Variant summary

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

The ENST00000502056.1(CASC8):​n.1042-16355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,014 control chromosomes in the GnomAD database, including 21,019 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 0.49 (21019 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 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.1042-16355G>A		intron	N/A
	CASC8	NR_117100.1		n.1041+19008G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1042-16355G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+19008G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73976 AN: 151896 Hom.: 21020 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.487 AC: 73977 AN: 152014 Hom.: 21019 Cov.: 32 AF XY: 0.489 AC XY: 36310 AN XY: 74322

African (AFR) AF: 0.175 AC: 7260 AN: 41466

American (AMR) AF: 0.558 AC: 8519 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1929 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2507 AN: 5172

South Asian (SAS) AF: 0.618 AC: 2982 AN: 4822

European-Finnish (FIN) AF: 0.571 AC: 6021 AN: 10538

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42787 AN: 67964

Other (OTH) AF: 0.529 AC: 1118 AN: 2112

Alfa AF: 0.587 Hom.: 47059

Bravo AF: 0.470

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.48
PhyloP100		-0.39

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: rs1447293;

hg19: chr8-128472320;