rs13282506

Positions:

• chr8-127446880-G-A
• chr8-127446880-G-C

Variant summary

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

The NR_117100.1(CASC8):​n.1042-25917C>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 0.227 in 152,066 control chromosomes in the GnomAD database, including 4,904 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 0.23 (4904 hom., cov: 32)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1042-25917C>T		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1042-3160C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1042-3160C>T		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1042-25917C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34422 AN: 151948 Hom.: 4889 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.227 AC: 34448 AN: 152066 Hom.: 4904 Cov.: 32 AF XY: 0.235 AC XY: 17482 AN XY: 74320

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.227

Alfa AF: 0.165 Hom.: 566

Bravo AF: 0.222

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13282506; hg19: chr8-128459125;