1-209432291-TAGCAGCAGCAGCAGCAGCAGCAGCAGC-TAGCAGCAGC

Variant names:

• chr1-209432291-TAGCAGCAGCAGCAGCAGC-T
• rs3842530
• ENST00000366437.8:n.662_679delGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000366437.8(MIR205HG):​n.662_679delGCAGCAGCAGCAGCAGCA 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 0.0052 in 1,333,098 control chromosomes in the GnomAD database, including 29 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (27 hom.)
• Consequence: MIR205HG ENST00000366437.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 10 publications found

Genes affected

MIR205HG (HGNC:43562): (MIR205 host gene)

MIR205 (HGNC:31583): (microRNA 205) 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR205HG	NR_145433.1	n.608_625delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 3 of 3
MIR205HG	NR_145434.1	n.743_760delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5
MIR205HG	NR_145435.1	n.691_708delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR205HG	ENST00000366437.8	n.662_679delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3
MIR205HG	ENST00000429156.7	n.773_790delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5	3
MIR205HG	ENST00000431096.7	n.694_711delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 709 AN: 149466 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00473

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00194

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00576

Gnomad OTH AF: 0.00632

GnomAD2 exomes AF: 0.00513 AC: 998 AN: 194576 AF XY: 0.00499

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00375

Gnomad ASJ exome AF: 0.00345

Gnomad EAS exome AF: 0.0000676

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.00566

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00525 AC: 6216 AN: 1183522 Hom.: 27 AF XY: 0.00515 AC XY: 3011 AN XY: 585108

African (AFR) AF: 0.00143 AC: 37 AN: 25904

American (AMR) AF: 0.00332 AC: 113 AN: 34058

Ashkenazi Jewish (ASJ) AF: 0.00307 AC: 50 AN: 16278

East Asian (EAS) AF: 0.00 AC: 0 AN: 16402

South Asian (SAS) AF: 0.00380 AC: 309 AN: 81276

European-Finnish (FIN) AF: 0.0132 AC: 396 AN: 30008

Middle Eastern (MID) AF: 0.0125 AC: 52 AN: 4160

European-Non Finnish (NFE) AF: 0.00536 AC: 4994 AN: 932534

Other (OTH) AF: 0.00618 AC: 265 AN: 42902

GnomAD4 genome AF: 0.00475 AC: 710 AN: 149576 Hom.: 2 Cov.: 0 AF XY: 0.00506 AC XY: 369 AN XY: 72964

African (AFR) AF: 0.00171 AC: 69 AN: 40276

American (AMR) AF: 0.00472 AC: 71 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 5 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00216 AC: 10 AN: 4630

European-Finnish (FIN) AF: 0.0144 AC: 149 AN: 10332

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00576 AC: 389 AN: 67530

Other (OTH) AF: 0.00625 AC: 13 AN: 2080

Alfa AF: 0.00349 Hom.: 2701

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3842530; hg19: chr1-209605636;