rs73159662

Variant names:

• chr7-129774728-G-A
• rs73159662
• ENST00000362288.1:n.42C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-129774728-G-A
• chr7-129774728-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

ENSG00000304993 (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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 163976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 662 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_029512.1. 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
	MIR96	NR_029512.1		n.42C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR183	NR_029615.1		n.*177C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR96	ENST00000362288.1	TSL:6	n.42C>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000304993	ENST00000807590.1		n.18G>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000286380	ENST00000710872.1		n.431+5062C>T		intron	N/A

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

GnomAD2 exomes AF: 0.00376 AC: 607 AN: 161364 AF XY: 0.00379

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 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

African (AFR) AF: 0.000994 AC: 9 AN: 9052

American (AMR) AF: 0.00339 AC: 93 AN: 27472

Ashkenazi Jewish (ASJ) AF: 0.000740 AC: 8 AN: 10806

East Asian (EAS) AF: 0.00273 AC: 27 AN: 9898

South Asian (SAS) AF: 0.000233 AC: 14 AN: 59974

European-Finnish (FIN) AF: 0.00285 AC: 79 AN: 27730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2728

European-Non Finnish (NFE) AF: 0.00584 AC: 935 AN: 160076

Other (OTH) AF: 0.00400 AC: 58 AN: 14504

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152240 Hom.: 2 Cov.: 33 AF XY: 0.00426 AC XY: 317 AN XY: 74424

African (AFR) AF: 0.00168 AC: 70 AN: 41554

American (AMR) AF: 0.00863 AC: 132 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00628 AC: 427 AN: 68016

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00526 Hom.: 2

Bravo AF: 0.00447

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		2.4
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

Other links and lift over

dbSNP: rs73159662; hg19: chr7-129414568;