Genetic Variant MIR27A:n.40A>G (chr19-13836478-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_029501.1(MIR27A):n.40A>G 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 0.344 in 537,596 control chromosomes in the GnomAD database, including 32,640 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 0.37 ( 11005 hom., cov: 33)

Exomes 𝑓: 0.33 ( 21635 hom. )

Consequence

MIR27A
NR_029501.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Variant links:

Genes affected

MIR27A (HGNC:31613): (microRNA 27a) 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]

MIR27A links:

MIR23AHG (HGNC:27620): (miR-23a/27a/24-2 cluster host gene)

MIR23AHG links:

MIR24-2 (HGNC:31608): (microRNA 24-2) 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]

MIR24-2 links:

MIR23A (HGNC:31605): (microRNA 23a) 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]

MIR23A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR27A	NR_029501.1 link	n.40A>G	non_coding_transcript_exon_variant	Exon 1 of 1
MIR23AHG	NR_036515.2 link	n.6441A>G	non_coding_transcript_exon_variant	Exon 1 of 1
MIR24-2	NR_029497.1 link	n.-119A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR27A	ENST00000385073.1 link	n.40A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR23AHG	ENST00000587762.2 link	n.6451A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR24-2	ENST00000386972.1 link	n.-119A>G	upstream_gene_variant		6
MIR23A	ENST00000385245.1 link	n.*109A>G	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56711

AN:

151970

Hom.:

10988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.335

AC:

81706

AN:

243584

Hom.:

13860

AF XY:

0.334

AC XY:

43985

AN XY:

131772

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.333

AC:

128355

AN:

385506

Hom.:

21635

Cov.:

AF XY:

0.333

AC XY:

72890

AN XY:

219050

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.287

Gnomad4 SAS exome

AF:

0.345

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.373

AC:

56761

AN:

152090

Hom.:

11005

Cov.:

AF XY:

0.371

AC XY:

27595

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.333

Hom.:

10455

Bravo

AF:

0.373

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over