rs9493099

chr6-131792263-T-C

Variant summary

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

The 6-131792263-T-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 154,418 control chromosomes in the GnomAD database, including 7,203 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 0.28 (7091 hom., cov: 32)
  • Exomes 𝑓: 0.29 (112 hom.)
• Consequence: MIR548H5 NR_039610.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

MIR548H5 (HGNC:41768): (microRNA 548h-5) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR548H5	NR_039610.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR548H5	ENST00000580314.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42388 AN: 152068 Hom.: 7084 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.346 AC: 141 AN: 408 Hom.: 29 AF XY: 0.359 AC XY: 84 AN XY: 234

Gnomad AFR exome AF: 0.500

Gnomad ASJ exome AF: 0.250

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.289 AC: 646 AN: 2232 Hom.: 112 Cov.: 0 AF XY: 0.300 AC XY: 335 AN XY: 1118

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.279 AC: 42405 AN: 152186 Hom.: 7091 Cov.: 32 AF XY: 0.289 AC XY: 21495 AN XY: 74394

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.302

Alfa AF: 0.300 Hom.: 14221

Bravo AF: 0.274

Asia WGS AF: 0.502 AC: 1742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.4
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9493099; hg19: chr6-132113403; COSMIC: COSV74123795;