rs60917039

chr11-74399290-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_039710.1(MIR548AL):n.54G>A 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 0.0145 in 154,432 control chromosomes in the GnomAD database, including 50 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 0.015 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (0 hom.)
• Consequence: MIR548AL NR_039710.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

MIR548AL (HGNC:41736): (microRNA 548al) 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2227/152276) while in subpopulation AFR AF= 0.0486 (2020/41564). AF 95% confidence interval is 0.0468. There are 50 homozygotes in gnomad4. There are 1016 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR548AL	NR_039710.1	n.54G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR548AL	ENST00000578416.1	n.54G>A		non_coding_transcript_exon_variant	1/1
	ENST00000524441.2	n.105+361G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000533008.1	n.154+1385G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2201 AN: 152158 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00881 AC: 19 AN: 2156 Hom.: 0 Cov.: 0 AF XY: 0.0103 AC XY: 11 AN XY: 1072

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0146 AC: 2227 AN: 152276 Hom.: 50 Cov.: 32 AF XY: 0.0136 AC XY: 1016 AN XY: 74446

Gnomad4 AFR AF: 0.0486

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.0103 Hom.: 4

Bravo AF: 0.0166

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	13
Dann	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60917039; hg19: chr11-74110335;