rs78825966

Variant names:

• chr1-168375591-C-T
• rs78825966
• ENST00000385239.1:n.68C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000293102 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030284.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR557	NR_030284.1		n.68C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR557	ENST00000385239.1	TSL:6	n.68C>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000293102	ENST00000636624.1	TSL:5	n.1358-382C>T		intron	N/A
	ENSG00000307038	ENST00000823032.1		n.139-4018C>T		intron	N/A

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

GnomAD2 exomes AF: 0.0135 AC: 3358 AN: 249494 AF XY: 0.00983

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 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

African (AFR) AF: 0.177 AC: 1848 AN: 10438

American (AMR) AF: 0.00818 AC: 295 AN: 36044

Ashkenazi Jewish (ASJ) AF: 0.000860 AC: 10 AN: 11628

East Asian (EAS) AF: 0.000304 AC: 4 AN: 13164

South Asian (SAS) AF: 0.000721 AC: 48 AN: 66578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32288

Middle Eastern (MID) AF: 0.0173 AC: 49 AN: 2832

European-Non Finnish (NFE) AF: 0.000793 AC: 152 AN: 191664

Other (OTH) AF: 0.00966 AC: 161 AN: 16668

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

African (AFR) AF: 0.175 AC: 7266 AN: 41498

American (AMR) AF: 0.0224 AC: 343 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68018

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.34
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs78825966; hg19: chr1-168344829;