8-127441683-T-C

Variant names:

• chr8-127441683-T-C
• rs12334695
• ENST00000502082.5:n.1042-20720A>G

Variant summary

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

The ENST00000502082.5(CASC8):​n.1042-20720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,108 control chromosomes in the GnomAD database, including 9,997 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 0.36 (9997 hom., cov: 32)
• Consequence: CASC8 ENST00000502082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1042-20720A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1042-20720A>G		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54419 AN: 151990 Hom.: 9991 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.358 AC: 54442 AN: 152108 Hom.: 9997 Cov.: 32 AF XY: 0.357 AC XY: 26546 AN XY: 74340

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.387

Alfa AF: 0.371 Hom.: 21832

Bravo AF: 0.350

Asia WGS AF: 0.275 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12334695; hg19: chr8-128453928;