rs12212674

chr6-22086845-T-A

Variant summary

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

The NR_015410.2(CASC15):n.1249-23902T>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 0.48 in 150,726 control chromosomes in the GnomAD database, including 18,289 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 (18289 hom., cov: 30)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1249-23902T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+30155T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72336 AN: 150630 Hom.: 18280 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.480 AC: 72357 AN: 150726 Hom.: 18289 Cov.: 30 AF XY: 0.477 AC XY: 35093 AN XY: 73558

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.458

Alfa AF: 0.515 Hom.: 2558

Bravo AF: 0.455

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	-0.91
Cadd	Benign	2.1
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12212674; hg19: chr6-22087074;