rs6981397

chr8-127443409-A-Gchr8-127443409-A-T

Variant summary

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

The ENST00000502056.1(CASC8):n.1353T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,106 control chromosomes in the GnomAD database, including 7,337 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 0.29 (7337 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC8 ENST00000502056.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1042-22446T>C		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1353T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1353T>C		non_coding_transcript_exon_variant	5/5	1
CASC8	ENST00000502082.5	n.1042-22446T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44234 AN: 151988 Hom.: 7324 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.282

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.291 AC: 44263 AN: 152106 Hom.: 7337 Cov.: 32 AF XY: 0.297 AC XY: 22077 AN XY: 74336

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.289

Alfa AF: 0.303 Hom.: 7829

Bravo AF: 0.282

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.1
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6981397; hg19: chr8-128455654;