rs7005829

Positions:

• chr8-127422699-C-T

Variant summary

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

The NR_117100.1(CASC8):​n.1042-1736G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,992 control chromosomes in the GnomAD database, including 5,934 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 0.28 (5934 hom., cov: 32)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1042-1736G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1042-1736G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41969 AN: 151874 Hom.: 5936 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.276 AC: 41980 AN: 151992 Hom.: 5934 Cov.: 32 AF XY: 0.278 AC XY: 20613 AN XY: 74260

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.291

Alfa AF: 0.252 Hom.: 1228

Bravo AF: 0.267

Asia WGS AF: 0.196 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7005829; hg19: chr8-128434944; COSMIC: COSV71838671;