ENST00000502082.5:n.1042-20557T>C

Variant names:

• chr8-127441520-A-G
• rs10090421
• ENST00000502082.5:n.1042-20557T>C

Variant summary

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

The ENST00000502082.5(CASC8):​n.1042-20557T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,004 control chromosomes in the GnomAD database, including 4,836 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 0.25 (4836 hom., cov: 31)
• Consequence: CASC8 ENST00000502082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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.1042-20557T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502082.5	TSL:1	n.1042-20557T>C		intron	N/A
	CASC8	ENST00000842817.1		n.-212T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37635 AN: 151886 Hom.: 4833 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.248 AC: 37648 AN: 152004 Hom.: 4836 Cov.: 31 AF XY: 0.249 AC XY: 18491 AN XY: 74278

African (AFR) AF: 0.261 AC: 10843 AN: 41466

American (AMR) AF: 0.198 AC: 3031 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1461 AN: 5158

South Asian (SAS) AF: 0.194 AC: 936 AN: 4818

European-Finnish (FIN) AF: 0.297 AC: 3136 AN: 10548

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16455 AN: 67954

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.245 Hom.: 7358

Bravo AF: 0.243

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.54
PhyloP100		-0.43

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: rs10090421;

hg19: chr8-128453765;