5-88643836-C-T

Variant summary

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

The NR_152235.1(LINC00461):n.218+27200G>A 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 0.162 in 151,722 control chromosomes in the GnomAD database, including 2,404 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 0.16 (2404 hom., cov: 32)
• Consequence: LINC00461 NR_152235.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC00461	NR_152235.1	n.218+27200G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC00461	ENST00000506978.5	n.265+27200G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24550 AN: 151604 Hom.: 2403 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.162 AC: 24563 AN: 151722 Hom.: 2404 Cov.: 32 AF XY: 0.162 AC XY: 12026 AN XY: 74142

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.161

Alfa AF: 0.136 Hom.: 208

Bravo AF: 0.173

Asia WGS AF: 0.262 AC: 907 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.24
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514301; hg19: chr5-87939654;