rs17421627

Positions:

• chr5-88551768-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_152235.1(LINC00461):​n.219-9698A>C variant causes a intron, non coding transcript change. The variant allele was found at a frequency of 0.0495 in 152,284 control chromosomes in the GnomAD database, including 256 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 0.050 (256 hom., cov: 32)
• Consequence: LINC00461 NR_152235.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.45

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC00461	NR_152235.1	n.219-9698A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC00461	ENST00000506978.5	n.266-9698A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7539 AN: 152166 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0495 AC: 7539 AN: 152284 Hom.: 256 Cov.: 32 AF XY: 0.0490 AC XY: 3647 AN XY: 74448

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0546

Alfa AF: 0.0676 Hom.: 461

Bravo AF: 0.0452

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17421627; hg19: chr5-87847586;