rs41280052

Variant names:

• chr15-79209826-G-T
• rs41280052
• ENST00000384962.1:n.39G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_029705.1(MIR184):​n.39G>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 0.0104 in 518,594 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 32)
  • Exomes 𝑓: 0.010 (32 hom.)
• Consequence: MIR184 NR_029705.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.615
• Publications: 14 publications found

Genes affected

MIR184 (HGNC:31555): (microRNA 184) 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 target mRNAs. This microRNA represents the most abundant miRNA in the corneal and lens epithelia of the eye and has been shown to interfere with target binding by another miRNA, miR-205. Through regulation of the VEGF and Akt signaling pathways, this microRNA may inhibit corneal angiogenesis. Mutations in the seed region of this microRNA cause familial keratoconus with cataract, also known as EDICT syndrome. [provided by RefSeq, Mar 2017]

ENSG00000292375 (HGNC:):

ANKRD34C-AS1 (HGNC:48618): (ANKRD34C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 15-79209826-G-T is Benign according to our data. Variant chr15-79209826-G-T is described in ClinVar as Benign. ClinVar VariationId is 1606846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1660/152320) while in subpopulation NFE AF = 0.0171 (1162/68030). AF 95% confidence interval is 0.0163. There are 12 homozygotes in GnomAd4. There are 774 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1660 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_029705.1. 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
	MIR184	NR_029705.1		n.39G>T		non_coding_transcript_exon	Exon 1 of 1
	ANKRD34C-AS1	NR_038997.1		n.298-17724C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR184	ENST00000384962.1	TSL:6	n.39G>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000292375	ENST00000711326.1		n.424G>T		non_coding_transcript_exon	Exon 1 of 2
	ANKRD34C-AS1	ENST00000559225.3	TSL:4	n.470+3361C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1660 AN: 152202 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00986 AC: 2469 AN: 250520 AF XY: 0.0100

Gnomad AFR exome AF: 0.00223

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.00637

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0156

Gnomad OTH exome AF: 0.00965

GnomAD4 exome AF: 0.0102 AC: 3723 AN: 366274 Hom.: 32 Cov.: 0 AF XY: 0.00961 AC XY: 2010 AN XY: 209182

African (AFR) AF: 0.00300 AC: 31 AN: 10344

American (AMR) AF: 0.00415 AC: 150 AN: 36180

Ashkenazi Jewish (ASJ) AF: 0.00631 AC: 72 AN: 11410

East Asian (EAS) AF: 0.00 AC: 0 AN: 12982

South Asian (SAS) AF: 0.000706 AC: 46 AN: 65134

European-Finnish (FIN) AF: 0.0165 AC: 524 AN: 31740

Middle Eastern (MID) AF: 0.00254 AC: 7 AN: 2754

European-Non Finnish (NFE) AF: 0.0152 AC: 2736 AN: 179956

Other (OTH) AF: 0.00995 AC: 157 AN: 15774

GnomAD4 genome AF: 0.0109 AC: 1660 AN: 152320 Hom.: 12 Cov.: 32 AF XY: 0.0104 AC XY: 774 AN XY: 74486

African (AFR) AF: 0.00274 AC: 114 AN: 41570

American (AMR) AF: 0.00712 AC: 109 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0169 AC: 179 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0171 AC: 1162 AN: 68030

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0122 Hom.: 3

Bravo AF: 0.00958

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs41280052; hg19: chr15-79502168;