6-21754983-G-A

Variant names:

• chr6-21754983-G-A
• rs7740168
• ENST00000606336.5:n.702-3410G>A

Variant summary

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

The ENST00000606336.5(CASC15):​n.702-3410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,034 control chromosomes in the GnomAD database, including 2,468 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 0.17 (2468 hom., cov: 32)
• Consequence: CASC15 ENST00000606336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 2 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]

LOC124901274 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606336.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	NR_015410.2		n.487-28649G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000606336.5	TSL:1	n.702-3410G>A		intron	N/A
	CASC15	ENST00000669942.1		n.786G>A		non_coding_transcript_exon	Exon 5 of 5
	CASC15	ENST00000822871.1		n.540G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25704 AN: 151916 Hom.: 2467 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0901

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.169 AC: 25724 AN: 152034 Hom.: 2468 Cov.: 32 AF XY: 0.162 AC XY: 12057 AN XY: 74316

African (AFR) AF: 0.250 AC: 10356 AN: 41426

American (AMR) AF: 0.135 AC: 2056 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3468

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5176

South Asian (SAS) AF: 0.0897 AC: 433 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1124 AN: 10576

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10735 AN: 67980

Other (OTH) AF: 0.163 AC: 343 AN: 2106

Alfa AF: 0.159 Hom.: 2248

Bravo AF: 0.174

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.87
DANN	Benign	0.67
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs7740168; hg19: chr6-21755214;