rs7012462

Positions:

• chr8-127445445-T-C

Variant summary

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

The ENST00000502056.1(CASC8):​n.1042-1725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,150 control chromosomes in the GnomAD database, including 30,313 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 0.63 (30313 hom., cov: 34)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

Genes affected

CASC8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_024393.1	n.1042-1725A>G		intron_variant
CASC8	NR_117100.1	n.1042-24482A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1	n.1042-1725A>G		intron_variant		1
CASC8	ENST00000502082.5	n.1042-24482A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95541 AN: 152032 Hom.: 30279 Cov.: 34

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.628 AC: 95622 AN: 152150 Hom.: 30313 Cov.: 34 AF XY: 0.624 AC XY: 46441 AN XY: 74374

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.612

Alfa AF: 0.598 Hom.: 25669

Bravo AF: 0.632

Asia WGS AF: 0.623 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7012462; hg19: chr8-128457690;