8-127458011-T-A

Variant names:

• chr8-127458011-T-A
• rs10956372
• ENST00000502056.1:n.1042-14291A>T

Variant summary

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

The ENST00000502056.1(CASC8):​n.1042-14291A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,098 control chromosomes in the GnomAD database, including 25,232 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 0.54 (25232 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.1042-14291A>T		intron	N/A
	CASC8	NR_117100.1		n.1041+21072A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1042-14291A>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1041+21072A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81703 AN: 151980 Hom.: 25232 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.537 AC: 81713 AN: 152098 Hom.: 25232 Cov.: 32 AF XY: 0.540 AC XY: 40151 AN XY: 74344

African (AFR) AF: 0.209 AC: 8675 AN: 41508

American (AMR) AF: 0.654 AC: 9991 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2753 AN: 5186

South Asian (SAS) AF: 0.656 AC: 3161 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6497 AN: 10536

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46314 AN: 67978

Other (OTH) AF: 0.575 AC: 1216 AN: 2116

Alfa AF: 0.581 Hom.: 3470

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.71
PhyloP100		-0.010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10956372; hg19: chr8-128470256;