8-127429378-C-T

Variant names:

• chr8-127429378-C-T
• rs7357486
• ENST00000502082.5:n.1042-8415G>A

Variant summary

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

The ENST00000502082.5(CASC8):​n.1042-8415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,056 control chromosomes in the GnomAD database, including 6,425 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 0.29 (6425 hom., cov: 32)
• Consequence: CASC8 ENST00000502082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 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.1042-8415G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502082.5	TSL:1	n.1042-8415G>A		intron	N/A
	CASC8	ENST00000842817.1		n.82-8415G>A		intron	N/A
	CASC8	ENST00000842818.1		n.137+5686G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43523 AN: 151938 Hom.: 6424 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.286 AC: 43544 AN: 152056 Hom.: 6425 Cov.: 32 AF XY: 0.287 AC XY: 21357 AN XY: 74346

African (AFR) AF: 0.308 AC: 12770 AN: 41464

American (AMR) AF: 0.220 AC: 3359 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1344 AN: 5180

South Asian (SAS) AF: 0.186 AC: 894 AN: 4816

European-Finnish (FIN) AF: 0.361 AC: 3817 AN: 10566

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18881 AN: 67960

Other (OTH) AF: 0.296 AC: 626 AN: 2112

Alfa AF: 0.273 Hom.: 1337

Bravo AF: 0.279

Asia WGS AF: 0.201 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.14

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: rs7357486;

hg19: chr8-128441623;