chr6-21754983-G-A

Position:

• chr6-21754983-G-A

Variant summary

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

The XR_007059492.1(LOC124901274):​n.173G>A variant causes a non coding transcript exon 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: LOC124901274 XR_007059492.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

Genes affected

LOC124901274 (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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901274	XR_007059492.1	n.173G>A		non_coding_transcript_exon_variant	2/2
CASC15	NR_015410.2	n.487-28649G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000688254.1	n.474-28649G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0897

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.163

Alfa AF: 0.157 Hom.: 1800

Bravo AF: 0.174

Asia WGS AF: 0.0460 AC: 160 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	0.87
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7740168; hg19: chr6-21755214;