rs515924

Positions:

• chr11-74399308-A-G

Variant summary

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

The NR_039710.1(MIR548AL):​n.72A>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 0.16 in 154,346 control chromosomes in the GnomAD database, including 2,204 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 0.16 (2190 hom., cov: 32)
  • Exomes 𝑓: 0.11 (14 hom.)
• Consequence: MIR548AL NR_039710.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR548AL	NR_039710.1	n.72A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR548AL	ENST00000578416.1	n.72A>G		mature_miRNA_variant	1/1
	ENST00000524441.2	n.105+379A>G		intron_variant, non_coding_transcript_variant		2
	ENST00000533008.1	n.154+1403A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24456 AN: 152058 Hom.: 2193 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.159 AC: 58 AN: 364 Hom.: 3 AF XY: 0.167 AC XY: 34 AN XY: 204

Gnomad AFR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.108 AC: 234 AN: 2170 Hom.: 14 Cov.: 0 AF XY: 0.105 AC XY: 113 AN XY: 1076

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.223

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.161 AC: 24458 AN: 152176 Hom.: 2190 Cov.: 32 AF XY: 0.169 AC XY: 12584 AN XY: 74400

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.134

Alfa AF: 0.144 Hom.: 1593

Bravo AF: 0.145

Asia WGS AF: 0.258 AC: 897 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: rs515924; hg19: chr11-74110353; COSMIC: COSV53347052;