rs78825966

Positions:

• chr1-168375591-C-T

Variant summary

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

The NR_030284.1(MIR557):​n.68C>T 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 0.0193 in 533,534 control chromosomes in the GnomAD database, including 822 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 0.051 (656 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (166 hom.)
• Consequence: MIR557 NR_030284.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

MIR557 (HGNC:32813): (microRNA 557) 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR557	NR_030284.1	n.68C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR557	ENST00000385239.1	n.68C>T		mature_miRNA_variant	1/1
	ENST00000636624.1	n.1358-382C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7725 AN: 152112 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0135 AC: 3358 AN: 249494 Hom.: 255 AF XY: 0.00983 AC XY: 1327 AN XY: 135052

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.00826

Gnomad ASJ exome AF: 0.00172

Gnomad EAS exome AF: 0.000382

Gnomad SAS exome AF: 0.000691

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000851

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00673 AC: 2567 AN: 381304 Hom.: 166 Cov.: 0 AF XY: 0.00514 AC XY: 1116 AN XY: 217134

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.00818

Gnomad4 ASJ exome AF: 0.000860

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.000721

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000793

Gnomad4 OTH exome AF: 0.00966

GnomAD4 genome AF: 0.0509 AC: 7751 AN: 152230 Hom.: 656 Cov.: 32 AF XY: 0.0505 AC XY: 3760 AN XY: 74434

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0259 Hom.: 118

Bravo AF: 0.0581

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78825966; hg19: chr1-168344829;