rs6999921

chr8-127428683-A-G

Variant summary

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

The NR_117100.1(CASC8):n.1042-7720T>C 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 0.0872 in 152,256 control chromosomes in the GnomAD database, including 642 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 0.087 (642 hom., cov: 32)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1042-7720T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1042-7720T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13252 AN: 152138 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0994

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

GnomAD4 genome AF: 0.0872 AC: 13280 AN: 152256 Hom.: 642 Cov.: 32 AF XY: 0.0856 AC XY: 6370 AN XY: 74438

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.0885 Hom.: 860

Bravo AF: 0.0887

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.4
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6999921; hg19: chr8-128440928;