chr6-21687911-A-G

Position:

• chr6-21687911-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.486+19012A>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 0.612 in 151,980 control chromosomes in the GnomAD database, including 28,922 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 0.61 (28922 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.486+19012A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.473+19012A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92980 AN: 151862 Hom.: 28884 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.612 AC: 93077 AN: 151980 Hom.: 28922 Cov.: 32 AF XY: 0.614 AC XY: 45556 AN XY: 74246

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.579

Alfa AF: 0.516 Hom.: 3032

Bravo AF: 0.627

Asia WGS AF: 0.708 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1475149; hg19: chr6-21688142;