8-127294819-C-T

Position:

• chr8-127294819-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000501396.5(CASC8):​n.687-4759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,264 control chromosomes in the GnomAD database, including 454 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 0.053 (454 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

CASC8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-27254C>T		intron_variant
CASC8	NR_117100.1	n.1177-4759G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.687-4759G>A		intron_variant		1
CASC8	ENST00000502082.5	n.1177-4759G>A		intron_variant		1
CASC8	ENST00000523825.2	n.547-4759G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7997 AN: 152146 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0526 AC: 8004 AN: 152264 Hom.: 454 Cov.: 32 AF XY: 0.0565 AC XY: 4209 AN XY: 74468

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0272 Hom.: 117

Bravo AF: 0.0558

Asia WGS AF: 0.192 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11994592; hg19: chr8-128307064;