rs41274239

Variant names:

• chr7-129774734-A-G
• rs41274239
• ENST00000362288.1:n.36T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NR_029512.1(MIR96):​n.36T>C variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 474,422 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (4 hom.)
• Consequence: MIR96 NR_029512.1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 8.60

Genes affected

MIR96 (HGNC:31648): (microRNA 96) 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]

ENSG00000286380 (HGNC:):

MIR183 (HGNC:31554): (microRNA 183) 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 7-129774734-A-G is Benign according to our data. Variant chr7-129774734-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 163977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-129774734-A-G is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR96	NR_029512.1	n.36T>C		non_coding_transcript_exon_variant	Exon 1 of 1
MIR96	unassigned_transcript_1306	n.-16T>C		upstream_gene_variant
MIR183	NR_029615.1	n.*171T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR96	ENST00000362288.1	n.36T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000286380	ENST00000710872.1	n.431+5056T>C		intron_variant	Intron 1 of 1
MIR183	ENST00000384958.1	n.*171T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152086 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00521

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00295 AC: 477 AN: 161596 Hom.: 3 AF XY: 0.00283 AC XY: 241 AN XY: 85152

Gnomad AFR exome AF: 0.000531

Gnomad AMR exome AF: 0.00140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000955

Gnomad FIN exome AF: 0.00601

Gnomad NFE exome AF: 0.00494

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00340 AC: 1095 AN: 322218 Hom.: 4 Cov.: 0 AF XY: 0.00317 AC XY: 577 AN XY: 181844

Gnomad4 AFR exome AF: 0.000662

Gnomad4 AMR exome AF: 0.00135

Gnomad4 ASJ exome AF: 0.0000925

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000734

Gnomad4 FIN exome AF: 0.00530

Gnomad4 NFE exome AF: 0.00511

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152204 Hom.: 4 Cov.: 33 AF XY: 0.00316 AC XY: 235 AN XY: 74422

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00521

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00395 Hom.: 1

Bravo AF: 0.00250

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 15, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MIR96: BS2 -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Oct 05, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

36T>C in Exon 1 of MIR96: This variant is not expected to have clinical signific ance because it has been identified in 0.7% (5/725) of American European and Eur opean chromosomes by the 1000 Genome Project (http://www.1000genomes.org/; dbSNP rs41274239) as well as 0.4% (28/7102) of European American chromosomes from a b road population by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/), and is not located in the seed region of the miRNA. -

Dec 06, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41274239; hg19: chr7-129414574;