rs41276930

Variant names:

• chr15-88611842-C-T
• rs41276930
• XM_017022489.2:c.-65+3000C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

Genes affected

AEN (HGNC:25722): (apoptosis enhancing nuclease) Enables exonuclease activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and response to ionizing radiation. Located in nuclear membrane; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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]

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_029606.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR7-2	NR_029606.1		n.18C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR3529	NR_039867.1		n.*5G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR7-2	ENST00000384970.1	TSL:6	n.18C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR3529	ENST00000637713.1	TSL:6	n.*5G>A		downstream_gene	N/A

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

GnomAD2 exomes AF: 0.00661 AC: 1520 AN: 230030 AF XY: 0.00731

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 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

African (AFR) AF: 0.000624 AC: 6 AN: 9618

American (AMR) AF: 0.00163 AC: 56 AN: 34286

Ashkenazi Jewish (ASJ) AF: 0.000704 AC: 8 AN: 11358

East Asian (EAS) AF: 0.0000861 AC: 1 AN: 11610

South Asian (SAS) AF: 0.0138 AC: 889 AN: 64190

European-Finnish (FIN) AF: 0.0349 AC: 1112 AN: 31872

Middle Eastern (MID) AF: 0.00886 AC: 18 AN: 2032

European-Non Finnish (NFE) AF: 0.00255 AC: 475 AN: 186118

Other (OTH) AF: 0.00826 AC: 133 AN: 16098

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

African (AFR) AF: 0.000409 AC: 17 AN: 41534

American (AMR) AF: 0.00406 AC: 62 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4822

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00301 AC: 205 AN: 67994

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.84
PhyloP100		-2.7

Splicing

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

Other links and lift over

dbSNP: rs41276930; hg19: chr15-89155073;