8-127428406-A-G

Variant names:

• chr8-127428406-A-G
• rs6995633
• ENST00000502082.5:n.1042-7443T>C

Variant summary

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

The ENST00000502082.5(CASC8):​n.1042-7443T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,268 control chromosomes in the GnomAD database, including 64,874 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 0.92 (64874 hom., cov: 32)
• Consequence: CASC8 ENST00000502082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 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.1042-7443T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502082.5	TSL:1	n.1042-7443T>C		intron	N/A
	CASC8	ENST00000842817.1		n.82-7443T>C		intron	N/A
	CASC8	ENST00000842818.1		n.137+6658T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140217 AN: 152150 Hom.: 64822 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.922 AC: 140329 AN: 152268 Hom.: 64874 Cov.: 32 AF XY: 0.919 AC XY: 68433 AN XY: 74466

African (AFR) AF: 0.976 AC: 40538 AN: 41546

American (AMR) AF: 0.838 AC: 12818 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3313 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4474 AN: 5172

South Asian (SAS) AF: 0.778 AC: 3753 AN: 4822

European-Finnish (FIN) AF: 0.957 AC: 10156 AN: 10608

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62185 AN: 68036

Other (OTH) AF: 0.924 AC: 1951 AN: 2112

Alfa AF: 0.913 Hom.: 211442

Bravo AF: 0.915

Asia WGS AF: 0.820 AC: 2856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.090
DANN	Benign	0.44
PhyloP100		-0.88

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: rs6995633;

hg19: chr8-128440651;