rs6470518

Positions:

• chr8-127471936-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+7147C>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 0.872 in 152,036 control chromosomes in the GnomAD database, including 57,902 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 (57902 hom., cov: 30)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10

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=-1.07).
• 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+7147C>T		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1041+7147C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1041+7147C>T		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+7147C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132421 AN: 151918 Hom.: 57867 Cov.: 30

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.872 AC: 132508 AN: 152036 Hom.: 57902 Cov.: 30 AF XY: 0.869 AC XY: 64594 AN XY: 74332

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.884

Alfa AF: 0.911 Hom.: 10967

Bravo AF: 0.873

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.068
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6470518; hg19: chr8-128484181;