rs9295535

Positions:

• chr6-10439735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_049872.1(MIR5689):​n.19T>C 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 0.2 in 147,136 control chromosomes in the GnomAD database, including 3,085 homozygotes. 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 0.20 (3082 hom., cov: 23)
  • Exomes 𝑓: 0.20 (3 hom.)
• Consequence: MIR5689 NR_049872.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

Genes affected

MIR5689 (HGNC:43479): (microRNA 5689) 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]

MIR5689HG (HGNC:52007): (MIR5689 host gene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR5689	NR_049872.1	n.19T>C		non_coding_transcript_exon_variant	1/1
MIR5689HG	NR_132993.1	n.76+5331T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR5689	ENST00000581998.1	n.19T>C		mature_miRNA_variant	1/1
MIR5689HG	ENST00000366312.2	n.76+5331T>C		intron_variant, non_coding_transcript_variant		3
MIR5689HG	ENST00000449333.1	n.89+5331T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29338 AN: 146954 Hom.: 3085 Cov.: 23

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.300 AC: 3 AN: 10 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad NFE exome AF: 0.300

GnomAD4 exome AF: 0.200 AC: 12 AN: 60 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 6 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.200 AC: 29345 AN: 147076 Hom.: 3082 Cov.: 23 AF XY: 0.201 AC XY: 14397 AN XY: 71766

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.199

Alfa AF: 0.217 Hom.: 948

Bravo AF: 0.199

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9295535; hg19: chr6-10439968;