chr7-129774728-G-A

Position:

chr7-129774728-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NR_029512.1(MIR96):n.42C>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 0.00397 in 474,480 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 4 hom. )

Consequence

MIR96
NR_029512.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.35

Variant links:

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]

MIR96 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 7-129774728-G-A is Benign according to our data. Variant chr7-129774728-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-129774728-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 662 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR96	NR_029512.1 linkuse as main transcript	n.42C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR96	ENST00000362288.1 linkuse as main transcript	n.42C>T		non_coding_transcript_exon_variant	1/1
	ENST00000710872.1 linkuse as main transcript	n.431+5062C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00435

AC:

662

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00376

AC:

607

AN:

161364

Hom.:

AF XY:

0.00379

AC XY:

322

AN XY:

85026

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.000585

Gnomad EAS exome

AF:

0.00207

Gnomad SAS exome

AF:

0.000304

Gnomad FIN exome

AF:

0.00320

Gnomad NFE exome

AF:

0.00636

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00380

AC:

1223

AN:

322240

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

640

AN XY:

181910

show subpopulations

Gnomad4 AFR exome

AF:

0.000994

Gnomad4 AMR exome

AF:

0.00339

Gnomad4 ASJ exome

AF:

0.000740

Gnomad4 EAS exome

AF:

0.00273

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.00584

Gnomad4 OTH exome

AF:

0.00400

GnomAD4 genome

AF:

0.00435

AC:

662

AN:

152240

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00628

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00526

Hom.:

Bravo

AF:

0.00447

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	MIR96: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 04, 2019	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 14, 2015	c.42C>T in exon 1 of MIR96: This variant is not expected to have clinical signif icance because it does not alter the seed region of the miRNA, is not located wi thin the splice consensus sequence, and has been identified in 0.3% (66/21086) o f chromosomes across multiple populations by the Exome Aggregation Consortium (E xAC, http://exac.broadinstitute.org; dbSNP rs73159662). -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2018	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

-0.32

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over