6-22451591-A-G

Variant names:

• chr6-22451591-A-G
• rs4560628
• ENST00000652081.2:n.145+98940A>G

Variant summary

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

The ENST00000652081.2(CASC15):​n.145+98940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,054 control chromosomes in the GnomAD database, including 42,210 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 0.74 (42210 hom., cov: 31)
• Consequence: CASC15 ENST00000652081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09
• Publications: 4 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]

LOC105374971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652081.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000652081.2		n.145+98940A>G		intron	N/A
	CASC15	ENST00000846434.1		n.347-66094A>G		intron	N/A
	CASC15	ENST00000846435.1		n.352-66094A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113178 AN: 151936 Hom.: 42173 Cov.: 31

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.745 AC: 113263 AN: 152054 Hom.: 42210 Cov.: 31 AF XY: 0.745 AC XY: 55389 AN XY: 74324

African (AFR) AF: 0.724 AC: 30031 AN: 41476

American (AMR) AF: 0.707 AC: 10809 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2664 AN: 3460

East Asian (EAS) AF: 0.850 AC: 4379 AN: 5154

South Asian (SAS) AF: 0.757 AC: 3646 AN: 4818

European-Finnish (FIN) AF: 0.749 AC: 7926 AN: 10576

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51458 AN: 67968

Other (OTH) AF: 0.726 AC: 1531 AN: 2110

Alfa AF: 0.750 Hom.: 79096

Bravo AF: 0.741

Asia WGS AF: 0.786 AC: 2730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.038
DANN	Benign	0.35
PhyloP100		-4.1

Splicing

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

Other links and lift over

dbSNP: rs4560628; hg19: chr6-22451820;