chr8-127453242-G-A

Variant names:

• chr8-127453242-G-A
• rs9643221
• ENST00000502056.1:n.1042-9522C>T

Variant summary

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

The ENST00000502056.1(CASC8):​n.1042-9522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,012 control chromosomes in the GnomAD database, including 8,724 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 0.30 (8724 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502056.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.1042-9522C>T		intron	N/A
	CASC8	NR_117100.1		n.1041+25841C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1042-9522C>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+25841C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46311 AN: 151892 Hom.: 8703 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.305 AC: 46357 AN: 152012 Hom.: 8724 Cov.: 32 AF XY: 0.307 AC XY: 22848 AN XY: 74316

African (AFR) AF: 0.502 AC: 20781 AN: 41420

American (AMR) AF: 0.369 AC: 5643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2682 AN: 5156

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2107 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12533 AN: 67952

Other (OTH) AF: 0.287 AC: 608 AN: 2116

Alfa AF: 0.274 Hom.: 1076

Bravo AF: 0.327

Asia WGS AF: 0.375 AC: 1300 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	0.58
DANN	Benign	0.36
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs9643221; hg19: chr8-128465487;