8-127462940-G-T

Variant names:

• chr8-127462940-G-T
• rs921146
• ENST00000502056.1:n.1041+16143C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502056.1(CASC8):​n.1041+16143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,002 control chromosomes in the GnomAD database, including 40,481 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 0.72 (40481 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_024393.1	n.1041+16143C>A		intron_variant	Intron 4 of 4
CASC8	NR_117100.1	n.1041+16143C>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1	n.1041+16143C>A		intron_variant	Intron 4 of 4	1
CASC8	ENST00000502082.5	n.1041+16143C>A		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109734 AN: 151884 Hom.: 40469 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.722 AC: 109786 AN: 152002 Hom.: 40481 Cov.: 32 AF XY: 0.723 AC XY: 53694 AN XY: 74294

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.730

Alfa AF: 0.783 Hom.: 63641

Bravo AF: 0.719

Asia WGS AF: 0.722 AC: 2502 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs921146; hg19: chr8-128475185;