X-145994784-T-G

Variant names:

• chrX-145994784-T-G
• rs5965660
• ENST00000401186.1:n.77A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000401186.1(MIR888):​n.77A>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 379,679 control chromosomes in the GnomAD database, including 3,112 homozygotes. There are 21,196 hemizygotes in GnomAD. 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 0.14 (883 hom., 4273 hem., cov: 23)
  • Exomes 𝑓: 0.16 (2229 hom. 16923 hem.)
• Consequence: MIR888 ENST00000401186.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 13 publications found

Genes affected

MIR888 (HGNC:33648): (microRNA 888) 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR888	NR_030592.1	n.77A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1
MIR888	unassigned_transcript_3835	n.*10A>C		downstream_gene_variant
MIR888	unassigned_transcript_3836	n.*46A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR888	ENST00000401186.1	n.77A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.135 AC: 15010 AN: 110925 Hom.: 885 Cov.: 23

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.142 AC: 24453 AN: 172252 AF XY: 0.148

Gnomad AFR exome AF: 0.0622

Gnomad AMR exome AF: 0.0620

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.0560

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.158 AC: 42556 AN: 268700 Hom.: 2229 Cov.: 0 AF XY: 0.161 AC XY: 16923 AN XY: 104930

African (AFR) AF: 0.0651 AC: 542 AN: 8325

American (AMR) AF: 0.0612 AC: 1740 AN: 28427

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 1083 AN: 8527

East Asian (EAS) AF: 0.0586 AC: 569 AN: 9715

South Asian (SAS) AF: 0.163 AC: 6375 AN: 39134

European-Finnish (FIN) AF: 0.183 AC: 4405 AN: 24065

Middle Eastern (MID) AF: 0.168 AC: 343 AN: 2040

European-Non Finnish (NFE) AF: 0.188 AC: 25563 AN: 136309

Other (OTH) AF: 0.159 AC: 1936 AN: 12158

GnomAD4 genome AF: 0.135 AC: 15001 AN: 110979 Hom.: 883 Cov.: 23 AF XY: 0.129 AC XY: 4273 AN XY: 33225

African (AFR) AF: 0.0645 AC: 1974 AN: 30617

American (AMR) AF: 0.0998 AC: 1045 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 323 AN: 2635

East Asian (EAS) AF: 0.0543 AC: 189 AN: 3478

South Asian (SAS) AF: 0.153 AC: 396 AN: 2584

European-Finnish (FIN) AF: 0.172 AC: 1019 AN: 5939

Middle Eastern (MID) AF: 0.166 AC: 35 AN: 211

European-Non Finnish (NFE) AF: 0.183 AC: 9668 AN: 52866

Other (OTH) AF: 0.120 AC: 180 AN: 1503

Alfa AF: 0.160 Hom.: 5271

Bravo AF: 0.129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.49
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs5965660; hg19: chrX-145076302; COSMIC: COSV107509035;