rs2078543

chr6-21996631-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.899+17569A>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 0.699 in 152,090 control chromosomes in the GnomAD database, including 37,462 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 0.70 (37462 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.899+17569A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.802+17569A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106194 AN: 151972 Hom.: 37457 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.699 AC: 106245 AN: 152090 Hom.: 37462 Cov.: 32 AF XY: 0.701 AC XY: 52159 AN XY: 74368

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.710

Alfa AF: 0.697 Hom.: 61320

Bravo AF: 0.703

Asia WGS AF: 0.860 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.15
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2078543; hg19: chr6-21996860;