rs10099905

Positions:

• chr8-127455689-A-C

Variant summary

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

The NR_117100.1(CASC8):​n.1041+23394T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,090 control chromosomes in the GnomAD database, including 47,945 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 0.79 (47945 hom., cov: 31)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1041+23394T>G		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1042-11969T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1042-11969T>G		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+23394T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120530 AN: 151972 Hom.: 47900 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.793 AC: 120637 AN: 152090 Hom.: 47945 Cov.: 31 AF XY: 0.797 AC XY: 59220 AN XY: 74344

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.810

Alfa AF: 0.791 Hom.: 49932

Bravo AF: 0.778

Asia WGS AF: 0.853 AC: 2965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10099905; hg19: chr8-128467934;