rs7000448

chr8-127428925-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.1042-7962G>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 0.445 in 151,824 control chromosomes in the GnomAD database, including 16,675 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 0.45 (16675 hom., cov: 31)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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 (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1042-7962G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1042-7962G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67517 AN: 151706 Hom.: 16653 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.445 AC: 67584 AN: 151824 Hom.: 16675 Cov.: 31 AF XY: 0.441 AC XY: 32681 AN XY: 74148

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.446

Alfa AF: 0.387 Hom.: 12000

Bravo AF: 0.448

Asia WGS AF: 0.285 AC: 995 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	0.22
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7000448; hg19: chr8-128441170;