8-127462940-G-T

Variant names:

• chr8-127462940-G-T
• rs921146
• ENST00000502056.1:n.1041+16143C>A

Variant summary

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

The ENST00000502056.1(CASC8):​n.1041+16143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,002 control chromosomes in the GnomAD database, including 40,481 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 0.72 (40481 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 11 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 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+16143C>A		intron	N/A
	CASC8	NR_117100.1		n.1041+16143C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1041+16143C>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+16143C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109734 AN: 151884 Hom.: 40469 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.722 AC: 109786 AN: 152002 Hom.: 40481 Cov.: 32 AF XY: 0.723 AC XY: 53694 AN XY: 74294

African (AFR) AF: 0.566 AC: 23420 AN: 41406

American (AMR) AF: 0.791 AC: 12085 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2652 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3765 AN: 5180

South Asian (SAS) AF: 0.809 AC: 3907 AN: 4828

European-Finnish (FIN) AF: 0.724 AC: 7630 AN: 10538

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53801 AN: 67980

Other (OTH) AF: 0.730 AC: 1541 AN: 2112

Alfa AF: 0.779 Hom.: 87142

Bravo AF: 0.719

Asia WGS AF: 0.722 AC: 2502 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.10
PhyloP100		-0.67

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: rs921146;

hg19: chr8-128475185;