rs6901423

Positions:

• chr6-22086063-A-G

Variant summary

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

The NR_015410.2(CASC15):​n.1249-24684A>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 0.478 in 151,888 control chromosomes in the GnomAD database, including 18,378 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 0.48 (18377 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

Genes affected

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-24684A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+29373A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72646 AN: 151764 Hom.: 18369 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.478 AC: 72667 AN: 151882 Hom.: 18377 Cov.: 32 AF XY: 0.475 AC XY: 35246 AN XY: 74218

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.459

Alfa AF: 0.525 Hom.: 5809

Bravo AF: 0.456

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6901423; hg19: chr6-22086292;