chr11-64891364-G-A

Variant names:

• chr11-64891364-G-A
• rs11231898
• ENST00000384864.1:n.76C>T

Variant summary

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

The ENST00000384864.1(MIR194-2):​n.76C>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 0.00725 in 521,136 control chromosomes in the GnomAD database, including 139 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 0.019 (106 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (33 hom.)
• Consequence: MIR194-2 ENST00000384864.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 10 publications found

Genes affected

MIR194-2 (HGNC:31565): (microRNA 194-2) 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]

MIR194-2HG (HGNC:51946): (MIR194-2 host gene)

MIR192 (HGNC:31562): (microRNA 192) 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000384864.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR194-2	NR_029829.1		n.76C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR194-2HG	NR_133638.1		n.1843C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR194-2HG	NR_133639.1		n.437+1065C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR194-2	ENST00000384864.1	TSL:6	n.76C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR194-2HG	ENST00000413053.2	TSL:2	n.1843C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR194-2HG	ENST00000710929.1		n.390+1226C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2838 AN: 152014 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00484 AC: 1090 AN: 225156 AF XY: 0.00353

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.00265

Gnomad EAS exome AF: 0.000469

Gnomad FIN exome AF: 0.0000524

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.00252

GnomAD4 exome AF: 0.00254 AC: 936 AN: 369004 Hom.: 33 Cov.: 0 AF XY: 0.00187 AC XY: 393 AN XY: 209762

African (AFR) AF: 0.0662 AC: 684 AN: 10326

American (AMR) AF: 0.00363 AC: 126 AN: 34682

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 27 AN: 11376

East Asian (EAS) AF: 0.000238 AC: 3 AN: 12594

South Asian (SAS) AF: 0.0000619 AC: 4 AN: 64598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30668

Middle Eastern (MID) AF: 0.00179 AC: 5 AN: 2796

European-Non Finnish (NFE) AF: 0.000178 AC: 33 AN: 185876

Other (OTH) AF: 0.00336 AC: 54 AN: 16088

GnomAD4 genome AF: 0.0187 AC: 2844 AN: 152132 Hom.: 106 Cov.: 32 AF XY: 0.0176 AC XY: 1311 AN XY: 74364

African (AFR) AF: 0.0642 AC: 2665 AN: 41484

American (AMR) AF: 0.00778 AC: 119 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67982

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00610 Hom.: 33

Bravo AF: 0.0209

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.4
DANN	Benign	0.88
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs11231898; hg19: chr11-64658836;