rs1447293

Positions:

• chr8-127460075-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.1041+19008G>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 0.487 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 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1041+19008G>A		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1042-16355G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1	n.1042-16355G>A		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+19008G>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.529

Alfa AF: 0.600 Hom.: 38679

Bravo AF: 0.470

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1447293; hg19: chr8-128472320;