rs6981424

Positions:

• chr8-127470851-G-A

Variant summary

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

The NR_117100.1(CASC8):​n.1041+8232C>T 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 0.307 in 151,902 control chromosomes in the GnomAD database, including 8,320 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 0.31 (8320 hom., cov: 32)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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 (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1041+8232C>T		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1041+8232C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502056.1	n.1041+8232C>T		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+8232C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46632 AN: 151784 Hom.: 8319 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.307 AC: 46633 AN: 151902 Hom.: 8320 Cov.: 32 AF XY: 0.305 AC XY: 22601 AN XY: 74210

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.322

Alfa AF: 0.380 Hom.: 12873

Bravo AF: 0.292

Asia WGS AF: 0.282 AC: 986 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	1.0
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6981424; hg19: chr8-128483096;