rs1047953

Positions:

• chr6-22186635-G-A
• chr6-22186635-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.1488-4932G>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 0.668 in 152,034 control chromosomes in the GnomAD database, including 36,176 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 0.67 (36176 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1488-4932G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1152-27672G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101546 AN: 151916 Hom.: 36169 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.668 AC: 101583 AN: 152034 Hom.: 36176 Cov.: 32 AF XY: 0.672 AC XY: 49989 AN XY: 74344

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.664

Alfa AF: 0.737 Hom.: 23533

Bravo AF: 0.652

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047953; hg19: chr6-22186864;