rs72631833

Variant names:

• chr7-129774964-C-A
• rs72631833
• ENST00000384958.1:n.51G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000384958.1(MIR183):​n.51G>T variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 529,310 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: MIR183 ENST00000384958.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.33
• Publications: 8 publications found

Genes affected

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]

ENSG00000286380 (HGNC:):

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 50

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 7-129774964-C-A is Benign according to our data. Variant chr7-129774964-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 163973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00514 (782/152278) while in subpopulation AFR AF = 0.0175 (727/41550). AF 95% confidence interval is 0.0164. There are 8 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000384958.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR183	NR_029615.1		n.51G>T		non_coding_transcript_exon	Exon 1 of 1
	MIR96	NR_029512.1		n.-195G>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR183	ENST00000384958.1	TSL:6	n.51G>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000286380	ENST00000710872.1		n.431+4826G>T		intron	N/A
	ENSG00000304993	ENST00000807590.1		n.174+80C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 779 AN: 152160 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00147 AC: 362 AN: 245768 AF XY: 0.00109

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.000993

GnomAD4 exome AF: 0.000713 AC: 269 AN: 377032 Hom.: 1 Cov.: 0 AF XY: 0.000580 AC XY: 124 AN XY: 213952

African (AFR) AF: 0.0178 AC: 186 AN: 10436

American (AMR) AF: 0.000998 AC: 36 AN: 36074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11620

East Asian (EAS) AF: 0.00 AC: 0 AN: 13032

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31862

Middle Eastern (MID) AF: 0.00149 AC: 4 AN: 2686

European-Non Finnish (NFE) AF: 0.000153 AC: 29 AN: 188932

Other (OTH) AF: 0.000789 AC: 13 AN: 16474

GnomAD4 genome AF: 0.00514 AC: 782 AN: 152278 Hom.: 8 Cov.: 33 AF XY: 0.00482 AC XY: 359 AN XY: 74458

African (AFR) AF: 0.0175 AC: 727 AN: 41550

American (AMR) AF: 0.00196 AC: 30 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68022

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00260 Hom.: 0

Bravo AF: 0.00583

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.92
PhyloP100		7.3

Splicing

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

Other links and lift over

dbSNP: rs72631833; hg19: chr7-129414804;