rs41276930

Positions:

• chr15-88611842-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NR_029606.1(MIR7-2):​n.18C>T 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 0.00664 in 519,372 control chromosomes in the GnomAD database, including 53 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 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (48 hom.)
• Consequence: MIR7-2 NR_029606.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

Genes affected

MIR7-2 (HGNC:31639): (microRNA 7-2) 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]

AEN (HGNC:):

MIR3529 (HGNC:41564): (microRNA 3529) 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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR7-2	NR_029606.1	n.18C>T		non_coding_transcript_exon_variant	1/1
MIR3529	NR_039867.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR7-2	ENST00000384970.1	n.18C>T		non_coding_transcript_exon_variant	1/1
MIR3529	ENST00000637713.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 752 AN: 152072 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00661 AC: 1520 AN: 230030 Hom.: 19 AF XY: 0.00731 AC XY: 912 AN XY: 124770

Gnomad AFR exome AF: 0.000349

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000629

Gnomad EAS exome AF: 0.000123

Gnomad SAS exome AF: 0.0129

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.00310

Gnomad OTH exome AF: 0.00873

GnomAD4 exome AF: 0.00735 AC: 2698 AN: 367182 Hom.: 48 Cov.: 0 AF XY: 0.00782 AC XY: 1638 AN XY: 209456

Gnomad4 AFR exome AF: 0.000624

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.000704

Gnomad4 EAS exome AF: 0.0000861

Gnomad4 SAS exome AF: 0.0138

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.00255

Gnomad4 OTH exome AF: 0.00826

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152190 Hom.: 5 Cov.: 32 AF XY: 0.00671 AC XY: 499 AN XY: 74392

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00406

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00293 Hom.: 2

Bravo AF: 0.00194

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41276930; hg19: chr15-89155073;