rs4560628

Positions:

• chr6-22451591-A-G
• chr6-22451591-A-T

Variant summary

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

The XR_001744024.2(LOC105374971):​n.482+50948A>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 0.745 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: LOC105374971 XR_001744024.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09

Genes affected

LOC105374971 (HGNC:):

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374971	XR_001744024.2	n.482+50948A>G		intron_variant, non_coding_transcript_variant
LOC105374971	XR_001744025.1	n.402+50948A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000652081.1	n.145+98940A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.726

Alfa AF: 0.751 Hom.: 58775

Bravo AF: 0.741

Asia WGS AF: 0.786 AC: 2730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4560628; hg19: chr6-22451820;