rs61992671

Variant names:

• chr14-101065517-A-G
• rs61992671
• ENST00000362142.2:n.71A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000362142.2(MIR412):​n.71A>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 0.367 in 534,354 control chromosomes in the GnomAD database, including 42,800 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 0.34 (11231 hom., cov: 32)
  • Exomes 𝑓: 0.38 (31569 hom.)
• Consequence: MIR412 ENST00000362142.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 36 publications found

Genes affected

MIR412 (HGNC:32064): (microRNA 412) 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]

MEG9 (HGNC:43874): (maternally expressed 9)

MIR369 (HGNC:31783): (microRNA 369) 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]

MIR409 (HGNC:32055): (microRNA 409) 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR412	NR_030155.1	n.71A>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR412	unassigned_transcript_2447	n.18A>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR369	NR_029862.1	n.-81A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR412	ENST00000362142.2	n.71A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MEG9	ENST00000699461.1	n.496+3910A>G		intron_variant	Intron 4 of 6
MEG9	ENST00000699462.1	n.219+1150A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51238 AN: 152012 Hom.: 11241 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.353 AC: 88479 AN: 250972 AF XY: 0.360

Gnomad AFR exome AF: 0.0928

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.0362

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.380 AC: 145135 AN: 382224 Hom.: 31569 Cov.: 0 AF XY: 0.374 AC XY: 81282 AN XY: 217552

African (AFR) AF: 0.0924 AC: 971 AN: 10510

American (AMR) AF: 0.212 AC: 7694 AN: 36304

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 5144 AN: 11742

East Asian (EAS) AF: 0.0353 AC: 465 AN: 13172

South Asian (SAS) AF: 0.231 AC: 15427 AN: 66764

European-Finnish (FIN) AF: 0.513 AC: 16570 AN: 32318

Middle Eastern (MID) AF: 0.383 AC: 1088 AN: 2838

European-Non Finnish (NFE) AF: 0.475 AC: 91109 AN: 191864

Other (OTH) AF: 0.399 AC: 6667 AN: 16712

GnomAD4 genome AF: 0.337 AC: 51227 AN: 152130 Hom.: 11231 Cov.: 32 AF XY: 0.335 AC XY: 24883 AN XY: 74358

African (AFR) AF: 0.0972 AC: 4039 AN: 41542

American (AMR) AF: 0.306 AC: 4678 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1552 AN: 3468

East Asian (EAS) AF: 0.0365 AC: 189 AN: 5176

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4816

European-Finnish (FIN) AF: 0.522 AC: 5513 AN: 10560

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32806 AN: 67952

Other (OTH) AF: 0.354 AC: 748 AN: 2114

Alfa AF: 0.396 Hom.: 9175

Bravo AF: 0.313

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.70
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs61992671; hg19: chr14-101531854; COSMIC: COSV62998420;