rs12197631

Positions:

• chr6-18571825-T-G

Variant summary

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

The NR_030312.1(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 NR_030312.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MIR548A1	NR_030312.1	n.42T>G		non_coding_transcript_exon_variant	1/1
MIR548A1HG	NR_149116.1	n.459-19150T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR548A1	ENST00000385041.1	n.42T>G		non_coding_transcript_exon_variant	1/1
MIR548A1HG	ENST00000637804.1	n.459-19150T>G		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0760 AC: 18193 AN: 239518 Hom.: 1145 AF XY: 0.0727 AC XY: 9491 AN XY: 130488

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 SAS exome AF: 0.103

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

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.0802

Gnomad4 ASJ exome AF: 0.0453

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0440

Gnomad4 NFE exome AF: 0.0493

Gnomad4 OTH exome AF: 0.0712

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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.0964

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.0404

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0743 Hom.: 150

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12197631; hg19: chr6-18572056;