8-127476954-T-C

Position:

• chr8-127476954-T-C

Variant summary

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

The ENST00000502056.1(CASC8):​n.1041+2129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 151,616 control chromosomes in the GnomAD database, including 64,326 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 (64326 hom., cov: 26)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

CASC8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_024393.1	n.1041+2129A>G		intron_variant
CASC8	NR_117100.1	n.1041+2129A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1	n.1041+2129A>G		intron_variant		1
CASC8	ENST00000502082.5	n.1041+2129A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139416 AN: 151502 Hom.: 64273 Cov.: 26

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.920 AC: 139525 AN: 151616 Hom.: 64326 Cov.: 26 AF XY: 0.917 AC XY: 67859 AN XY: 74008

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.920

Alfa AF: 0.903 Hom.: 7245

Bravo AF: 0.929

Asia WGS AF: 0.824 AC: 2867 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	1.6
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7826179; hg19: chr8-128489199;