rs531564

Variant names:

• chr8-9903189-G-C
• rs531564
• ENST00000519461.2:n.210C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000519461.2(MIR124-1HG):​n.210C>G 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 0.124 in 352,428 control chromosomes in the GnomAD database, including 2,940 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 0.13 (1486 hom., cov: 33)
  • Exomes 𝑓: 0.12 (1454 hom.)
• Consequence: MIR124-1HG ENST00000519461.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 104 publications found

Genes affected

MIR124-1HG (HGNC:27231): (MIR124-1 host gene) Predicted to act upstream of or within several processes, including gene silencing by miRNA; long-term synaptic potentiation; and sensory perception of sound. [provided by Alliance of Genome Resources, Apr 2022]

MIR124-1 (HGNC:31502): (microRNA 124-1) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR124-1HG	NR_024281.1	n.141C>G		non_coding_transcript_exon_variant	Exon 1 of 3
MIR124-1	NR_029668.1	n.*199C>G		downstream_gene_variant
MIR124-1	unassigned_transcript_1448	n.*210C>G		downstream_gene_variant
MIR124-1	unassigned_transcript_1449	n.*249C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR124-1HG	ENST00000519461.2	n.210C>G		non_coding_transcript_exon_variant	Exon 1 of 3	1
MIR124-1HG	ENST00000517675.2	n.209C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR124-1HG	ENST00000521863.2	n.587C>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20522 AN: 152066 Hom.: 1479 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.115 AC: 23052 AN: 200244 Hom.: 1454 Cov.: 0 AF XY: 0.109 AC XY: 12057 AN XY: 110902

African (AFR) AF: 0.168 AC: 818 AN: 4864

American (AMR) AF: 0.0842 AC: 926 AN: 10998

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 372 AN: 4282

East Asian (EAS) AF: 0.148 AC: 1178 AN: 7934

South Asian (SAS) AF: 0.0673 AC: 2892 AN: 42988

European-Finnish (FIN) AF: 0.149 AC: 1336 AN: 8968

Middle Eastern (MID) AF: 0.120 AC: 79 AN: 660

European-Non Finnish (NFE) AF: 0.130 AC: 14297 AN: 110042

Other (OTH) AF: 0.121 AC: 1154 AN: 9508

GnomAD4 genome AF: 0.135 AC: 20541 AN: 152184 Hom.: 1486 Cov.: 33 AF XY: 0.133 AC XY: 9871 AN XY: 74396

African (AFR) AF: 0.165 AC: 6832 AN: 41518

American (AMR) AF: 0.101 AC: 1541 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.139 AC: 715 AN: 5156

South Asian (SAS) AF: 0.0665 AC: 320 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1725 AN: 10598

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8687 AN: 68010

Other (OTH) AF: 0.121 AC: 256 AN: 2110

Alfa AF: 0.131 Hom.: 164

Bravo AF: 0.132

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.037

Splicing

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

Other links and lift over

dbSNP: rs531564; hg19: chr8-9760699; COSMIC: COSV66118674;