rs2304608

Positions:

• chr5-88666480-C-A
• chr5-88666480-C-G

Variant summary

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

The ENST00000500197.6(LINC00461):​n.1346G>T 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 0.202 in 224,762 control chromosomes in the GnomAD database, including 5,332 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 0.21 (3909 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1423 hom.)
• Consequence: LINC00461 ENST00000500197.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

Genes affected

LINC00461 (HGNC:42810): (MIR9-2 host gene) This is an evolutionarily conserved gene that produces alternatively spliced long non-coding RNAs that may be expressed predominantly in the brain and visual cortex. These transcripts may be involved in tumorigenesis, as depletion by siRNA suppressed glioma cell division. Transcripts may also bind to and regulate the activity of miR-411-5p and argonaut 2, thereby altering the expression of genes involved in tumor growth. [provided by RefSeq, Nov 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC00461	NR_152235.1	n.218+4556G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC00461	ENST00000506978.5	n.265+4556G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32379 AN: 151774 Hom.: 3912 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.180 AC: 13108 AN: 72870 Hom.: 1423 Cov.: 0 AF XY: 0.191 AC XY: 7476 AN XY: 39152

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.213 AC: 32397 AN: 151892 Hom.: 3909 Cov.: 32 AF XY: 0.213 AC XY: 15798 AN XY: 74228

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.212

Alfa AF: 0.187 Hom.: 376

Bravo AF: 0.224

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2304608; hg19: chr5-87962298;