22-21653345-G-T

Position:

• chr22-21653345-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_029845.1(MIR130B):​n.42G>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 0.00118 in 510,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: MIR130B NR_029845.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

Genes affected

MIR130B (HGNC:31515): (microRNA 130b) 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]

LOC107985532 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR130B	NR_029845.1	n.42G>T		non_coding_transcript_exon_variant	1/1
LOC107985532	NR_169730.1	n.155G>T		non_coding_transcript_exon_variant	2/5
LOC107985532	NR_169729.1	n.155G>T		non_coding_transcript_exon_variant	2/7
LOC107985532	NR_169731.1	n.155G>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR130B	ENST00000385018.1	n.42G>T		non_coding_transcript_exon_variant	1/1
	ENST00000701182.1	n.152G>T		non_coding_transcript_exon_variant	2/4
	ENST00000701082.1	n.149-668G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00125 AC: 258 AN: 205910 Hom.: 0 AF XY: 0.00109 AC XY: 121 AN XY: 111196

Gnomad AFR exome AF: 0.000162

Gnomad AMR exome AF: 0.000679

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00211

Gnomad NFE exome AF: 0.00220

Gnomad OTH exome AF: 0.000579

GnomAD4 exome AF: 0.00129 AC: 463 AN: 358032 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 220 AN XY: 203518

Gnomad4 AFR exome AF: 0.000100

Gnomad4 AMR exome AF: 0.000625

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00194

Gnomad4 NFE exome AF: 0.00199

Gnomad4 OTH exome AF: 0.00153

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65 AN XY: 74470

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000747 Hom.: 0

Bravo AF: 0.00102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72631822; hg19: chr22-22007634;