6-21687911-A-G

Variant names:

• chr6-21687911-A-G
• rs1475149
• ENST00000606336.5:n.575+19012A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000606336.5(CASC15):​n.575+19012A>G variant causes a intron 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 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.486+19012A>G		intron_variant	Intron 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000606336.5	n.575+19012A>G		intron_variant	Intron 3 of 6	1
CASC15	ENST00000606851.5	n.455+19012A>G		intron_variant	Intron 2 of 11	2
CASC15	ENST00000607048.5	n.81+19012A>G		intron_variant	Intron 1 of 11	2

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

African (AFR) AF: 0.679 AC: 28133 AN: 41450

American (AMR) AF: 0.677 AC: 10347 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3464

East Asian (EAS) AF: 0.809 AC: 4163 AN: 5144

South Asian (SAS) AF: 0.538 AC: 2586 AN: 4806

European-Finnish (FIN) AF: 0.596 AC: 6291 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38110 AN: 67962

Other (OTH) AF: 0.579 AC: 1224 AN: 2114

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
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs1475149; hg19: chr6-21688142;