8-127446399-C-T

Variant names:

• chr8-127446399-C-T
• rs4871791
• ENST00000502056.1:n.1042-2679G>A

Variant summary

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

The ENST00000502056.1(CASC8):​n.1042-2679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,088 control chromosomes in the GnomAD database, including 16,280 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 (16280 hom., cov: 33)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.817 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.1042-2679G>A		intron	N/A
	CASC8	NR_117100.1		n.1042-25436G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1042-2679G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1042-25436G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68733 AN: 151970 Hom.: 16271 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.452 AC: 68774 AN: 152088 Hom.: 16280 Cov.: 33 AF XY: 0.460 AC XY: 34163 AN XY: 74336

African (AFR) AF: 0.343 AC: 14251 AN: 41490

American (AMR) AF: 0.511 AC: 7812 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3468

East Asian (EAS) AF: 0.838 AC: 4340 AN: 5182

South Asian (SAS) AF: 0.454 AC: 2182 AN: 4808

European-Finnish (FIN) AF: 0.544 AC: 5742 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31313 AN: 67982

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.447 Hom.: 37558

Bravo AF: 0.444

Asia WGS AF: 0.614 AC: 2132 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	2.9
DANN	Benign	0.73
PhyloP100		0.15

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: rs4871791;

hg19: chr8-128458644;