8-127472088-T-C

Variant names:

• chr8-127472088-T-C
• rs6470520
• ENST00000502056.1:n.1041+6995A>G

Variant summary

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

The ENST00000502056.1(CASC8):​n.1041+6995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,212 control chromosomes in the GnomAD database, including 55,136 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 0.85 (55136 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• 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 (AMR) allele frequency at 95% confidence interval = 0.893 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.1041+6995A>G		intron	N/A
	CASC8	NR_117100.1		n.1041+6995A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1041+6995A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+6995A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128972 AN: 152094 Hom.: 55123 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.848 AC: 129029 AN: 152212 Hom.: 55136 Cov.: 32 AF XY: 0.847 AC XY: 62999 AN XY: 74402

African (AFR) AF: 0.733 AC: 30441 AN: 41502

American (AMR) AF: 0.906 AC: 13863 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3265 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4413 AN: 5188

South Asian (SAS) AF: 0.872 AC: 4207 AN: 4824

European-Finnish (FIN) AF: 0.825 AC: 8730 AN: 10584

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61169 AN: 68026

Other (OTH) AF: 0.871 AC: 1837 AN: 2110

Alfa AF: 0.884 Hom.: 28415

Bravo AF: 0.846

Asia WGS AF: 0.803 AC: 2794 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	6.5
DANN	Benign	0.49
PhyloP100		-0.32

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: rs6470520;

hg19: chr8-128484333;