ENST00000444265.6:n.1062-39711A>G

Variant names:

• chr6-22151856-A-G
• rs6916371
• ENST00000444265.6:n.1062-39711A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.1062-39711A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,208 control chromosomes in the GnomAD database, including 65,802 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 0.93 (65802 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1423-22142A>G		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1062-39711A>G		intron_variant	Intron 7 of 10	1
CASC15	ENST00000561912.3	n.199+4786A>G		intron_variant	Intron 1 of 10	5
CASC15	ENST00000567753.2	n.88+4786A>G		intron_variant	Intron 1 of 2	6

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140888 AN: 152090 Hom.: 65767 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.926 AC: 140974 AN: 152208 Hom.: 65802 Cov.: 32 AF XY: 0.922 AC XY: 68612 AN XY: 74410

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.963

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.938

Alfa AF: 0.960 Hom.: 8827

Bravo AF: 0.913

Asia WGS AF: 0.816 AC: 2828 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6916371; hg19: chr6-22152085;