rs12197631

Variant names:

• chr6-18571825-T-G
• rs12197631
• ENST00000385041.1:n.42T>G

Variant summary

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

The ENST00000385041.1(MIR548A1):​n.42T>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 0.0829 in 526,252 control chromosomes in the GnomAD database, including 3,159 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 0.12 (1863 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1296 hom.)
• Consequence: MIR548A1 ENST00000385041.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 13 publications found

Genes affected

MIR548A1 (HGNC:32796): (microRNA 548a-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]

MIR548A1HG (HGNC:53539): (MIR548A1 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR548A1	NR_030312.1	n.42T>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR548A1HG	NR_149116.1	n.459-19150T>G		intron_variant	Intron 3 of 7
MIR548A1	unassigned_transcript_945	n.-19T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR548A1	ENST00000385041.1	n.42T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR548A1HG	ENST00000637804.1	n.459-19150T>G		intron_variant	Intron 3 of 5	5
MIR548A1HG	ENST00000835487.1	n.543-19150T>G		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17933 AN: 152122 Hom.: 1865 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.0760 AC: 18193 AN: 239518 AF XY: 0.0727

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.0799

Gnomad ASJ exome AF: 0.0458

Gnomad EAS exome AF: 0.0438

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0502

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0687 AC: 25694 AN: 374012 Hom.: 1296 Cov.: 0 AF XY: 0.0701 AC XY: 14982 AN XY: 213830

African (AFR) AF: 0.271 AC: 2847 AN: 10502

American (AMR) AF: 0.0802 AC: 2906 AN: 36226

Ashkenazi Jewish (ASJ) AF: 0.0453 AC: 532 AN: 11742

East Asian (EAS) AF: 0.0434 AC: 568 AN: 13098

South Asian (SAS) AF: 0.104 AC: 6945 AN: 66716

European-Finnish (FIN) AF: 0.0440 AC: 1069 AN: 24294

Middle Eastern (MID) AF: 0.0654 AC: 186 AN: 2844

European-Non Finnish (NFE) AF: 0.0493 AC: 9455 AN: 191938

Other (OTH) AF: 0.0712 AC: 1186 AN: 16652

GnomAD4 genome AF: 0.118 AC: 17948 AN: 152240 Hom.: 1863 Cov.: 32 AF XY: 0.116 AC XY: 8642 AN XY: 74442

African (AFR) AF: 0.279 AC: 11568 AN: 41504

American (AMR) AF: 0.0964 AC: 1475 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5180

South Asian (SAS) AF: 0.0998 AC: 482 AN: 4830

European-Finnish (FIN) AF: 0.0404 AC: 429 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3366 AN: 68018

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.0788 Hom.: 180

Bravo AF: 0.128

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.77
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs12197631; hg19: chr6-18572056;