7-129774728-G-A

Position:

• chr7-129774728-G-A

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.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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.35

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]

(HGNC:):

ACMG classification

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	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	n.42C>T		non_coding_transcript_exon_variant	1/1
	ENST00000710872.1	n.431+5062C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00435 AC: 662 AN: 152122 Hom.: 2 Cov.: 33

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.: 2 AF XY: 0.00379 AC XY: 322 AN XY: 85026

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.: 4 Cov.: 0 AF XY: 0.00352 AC XY: 640 AN XY: 181910

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.: 2 Cov.: 33 AF XY: 0.00426 AC XY: 317 AN XY: 74424

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.: 2

Bravo AF: 0.00447

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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	18
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

Other links and lift over

dbSNP: rs73159662; hg19: chr7-129414568;