rs7000448

Variant names:

• chr8-127428925-C-T
• rs7000448
• ENST00000502082.5:n.1042-7962G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502082.5(CASC8):​n.1042-7962G>A variant causes a intron 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 ENST00000502082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 60 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502082.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1042-7962G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502082.5	TSL:1	n.1042-7962G>A		intron	N/A
	CASC8	ENST00000842817.1		n.82-7962G>A		intron	N/A
	CASC8	ENST00000842818.1		n.137+6139G>A		intron	N/A

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

African (AFR) AF: 0.667 AC: 27613 AN: 41398

American (AMR) AF: 0.319 AC: 4863 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1659 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1527 AN: 5160

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4806

European-Finnish (FIN) AF: 0.435 AC: 4555 AN: 10482

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.363 AC: 24653 AN: 67926

Other (OTH) AF: 0.446 AC: 941 AN: 2112

Alfa AF: 0.393 Hom.: 35352

Bravo AF: 0.448

Asia WGS AF: 0.285 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.39
PhyloP100		-0.21

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7000448;

hg19: chr8-128441170;