rs9393227

Positions:

• chr6-22100683-G-A
• chr6-22100683-G-C
• chr6-22100683-G-T

Variant summary

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

The NR_015410.2(CASC15):​n.1249-10064G>A 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 0.633 in 151,992 control chromosomes in the GnomAD database, including 31,070 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 0.63 (31070 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1249-10064G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+43993G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96070 AN: 151874 Hom.: 31043 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.633 AC: 96147 AN: 151992 Hom.: 31070 Cov.: 32 AF XY: 0.641 AC XY: 47607 AN XY: 74294

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.590

Alfa AF: 0.579 Hom.: 15386

Bravo AF: 0.632

Asia WGS AF: 0.690 AC: 2396 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9393227; hg19: chr6-22100912;