chr6-22150129-G-A

Position:

• chr6-22150129-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_015410.2(CASC15):​n.1423-23869G>A variant causes a intron, non coding transcript change. The variant allele was found at a frequency of 0.106 in 152,138 control chromosomes in the GnomAD database, including 1,110 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 0.11 (1110 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1423-23869G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000688254.1	n.1152-64178G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16202 AN: 152018 Hom.: 1114 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.0986

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.106 AC: 16187 AN: 152136 Hom.: 1110 Cov.: 32 AF XY: 0.106 AC XY: 7913 AN XY: 74380

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.0977

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.136 Hom.: 2179

Bravo AF: 0.0948

Asia WGS AF: 0.0470 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498705; hg19: chr6-22150358;