ENST00000385073.1:n.40A>G

Variant names:

• chr19-13836478-T-C
• rs895819
• ENST00000385073.1:n.40A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000385073.1(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 ENST00000385073.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 291 publications found

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]

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

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]

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]

ENSG00000302686 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR27A	NR_029501.1	n.40A>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR23AHG	NR_036515.2	n.6441A>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR24-2	NR_029497.1	n.-119A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR27A	ENST00000385073.1	n.40A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR23AHG	ENST00000587762.2	n.6451A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR24-2	ENST00000386972.1	n.-119A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56711 AN: 151970 Hom.: 10988 Cov.: 33

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

GnomAD2 exomes AF: 0.335 AC: 81706 AN: 243584 AF XY: 0.334

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 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.: 0 AF XY: 0.333 AC XY: 72890 AN XY: 219050

African (AFR) AF: 0.500 AC: 5314 AN: 10634

American (AMR) AF: 0.312 AC: 11151 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 3167 AN: 11738

East Asian (EAS) AF: 0.287 AC: 3996 AN: 13902

South Asian (SAS) AF: 0.345 AC: 22865 AN: 66244

European-Finnish (FIN) AF: 0.360 AC: 11837 AN: 32846

Middle Eastern (MID) AF: 0.267 AC: 764 AN: 2862

European-Non Finnish (NFE) AF: 0.327 AC: 63709 AN: 194640

Other (OTH) AF: 0.328 AC: 5552 AN: 16934

GnomAD4 genome AF: 0.373 AC: 56761 AN: 152090 Hom.: 11005 Cov.: 33 AF XY: 0.371 AC XY: 27595 AN XY: 74354

African (AFR) AF: 0.495 AC: 20554 AN: 41488

American (AMR) AF: 0.329 AC: 5024 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1480 AN: 5158

South Asian (SAS) AF: 0.327 AC: 1581 AN: 4828

European-Finnish (FIN) AF: 0.370 AC: 3924 AN: 10598

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22273 AN: 67952

Other (OTH) AF: 0.316 AC: 668 AN: 2114

Alfa AF: 0.338 Hom.: 14397

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	15
DANN	Benign	0.69
PhyloP100		0.25
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

Other links and lift over

dbSNP: rs895819; hg19: chr19-13947292; COSMIC: COSV54321327;