rs6470519

Positions:

• chr8-127471978-A-C
• chr8-127471978-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.1041+7105T>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 0.871 in 152,098 control chromosomes in the GnomAD database, including 57,930 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 0.87 (57930 hom., cov: 31)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1041+7105T>G		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1041+7105T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1041+7105T>G		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+7105T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132459 AN: 151982 Hom.: 57897 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.871 AC: 132543 AN: 152098 Hom.: 57930 Cov.: 31 AF XY: 0.869 AC XY: 64574 AN XY: 74324

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.883

Alfa AF: 0.898 Hom.: 65466

Bravo AF: 0.873

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6470519; hg19: chr8-128484223;