Genetic Variant LINC00323:n.254+900delG (chr21-41167642-AC-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000435493.3(LINC00323):n.254+900delG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 6829 hom., cov: 0)

Exomes 𝑓: 0.38 ( 58 hom. )

Consequence

LINC00323
ENST00000435493.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.439

Publications

2 publications found

Variant links:

COSMIC-nc: COSV57739317

Genes affected

LINC00323 (HGNC:19720): (long intergenic non-protein coding RNA 323)

LINC00323 links:

BACE2 (HGNC:934): (beta-secretase 2) This gene encodes an integral membrane glycoprotein that functions as an aspartic protease. The encoded protein cleaves amyloid precursor protein into amyloid beta peptide, which is a critical step in the etiology of Alzheimer's disease and Down syndrome. The protein precursor is further processed into an active mature peptide. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

BACE2 links:

MIR3197 (HGNC:38366): (microRNA 3197) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3197 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR3197	NR_036167.1 link	n.*14delC		downstream_gene_variant
MIR3197	unassigned_transcript_3528	n.*57delC		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LINC00323	ENST00000435493.3 link	n.254+900delG	intron_variant	Intron 1 of 3	3
LINC00323	ENST00000836835.1 link	n.246+900delG	intron_variant	Intron 1 of 3
LINC00323	ENST00000836836.1 link	n.167+900delG	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44925

AN:

151044

Hom.:

6809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.292

GnomAD2 exomes

AF:

0.324

AC:

447

AN:

1380

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.250

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.384

AC:

356

AN:

926

Hom.:

Cov.:

AF XY:

0.381

AC XY:

170

AN XY:

446

show subpopulations

African (AFR)

AF:

0.450

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.571

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.444

AC:

237

AN:

534

European-Non Finnish (NFE)

AF:

0.268

AC:

AN:

250

Other (OTH)

AF:

0.329

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.298

AC:

44976

AN:

151154

Hom.:

6829

Cov.:

AF XY:

0.300

AC XY:

22159

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.326

AC:

13450

AN:

41212

American (AMR)

AF:

0.327

AC:

4993

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1353

AN:

3464

East Asian (EAS)

AF:

0.315

AC:

1586

AN:

5032

South Asian (SAS)

AF:

0.461

AC:

2203

AN:

4776

European-Finnish (FIN)

AF:

0.249

AC:

2621

AN:

10508

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.263

AC:

17796

AN:

67626

Other (OTH)

AF:

0.300

AC:

629

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1617

3235

4852

6470

8087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.280

Hom.:

733

Bravo

AF:

0.298

Asia WGS

AF:

0.399

AC:

1385

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.44

Splicing

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

Publications

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21-41167642-ACC-AC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over