1-209432291-TAGCAGCAGCAGCAGCAGCAGCAGCAGC-TAGCAGCAGCAGCAGC

Variant names:

• chr1-209432291-TAGCAGCAGCAGC-T
• rs3842530
• ENST00000366437.8:n.668_679delGCAGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000366437.8(MIR205HG):​n.668_679delGCAGCAGCAGCA 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 0.618 in 1,332,644 control chromosomes in the GnomAD database, including 259,280 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 0.53 (24311 hom., cov: 0)
  • Exomes 𝑓: 0.63 (234969 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR205HG	NR_145433.1	n.614_625delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 3 of 3
MIR205HG	NR_145434.1	n.749_760delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5
MIR205HG	NR_145435.1	n.697_708delGCAGCAGCAGCA		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.668_679delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3
MIR205HG	ENST00000429156.7	n.779_790delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5	3
MIR205HG	ENST00000431096.7	n.700_711delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 79665 AN: 149280 Hom.: 24300 Cov.: 0

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.602 AC: 117179 AN: 194576 AF XY: 0.605

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.675

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.629 AC: 744513 AN: 1183254 Hom.: 234969 AF XY: 0.628 AC XY: 367623 AN XY: 584962

African (AFR) AF: 0.166 AC: 4296 AN: 25902

American (AMR) AF: 0.660 AC: 22475 AN: 34052

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 10999 AN: 16272

East Asian (EAS) AF: 0.701 AC: 11502 AN: 16400

South Asian (SAS) AF: 0.619 AC: 50303 AN: 81258

European-Finnish (FIN) AF: 0.595 AC: 17843 AN: 29982

Middle Eastern (MID) AF: 0.601 AC: 2497 AN: 4156

European-Non Finnish (NFE) AF: 0.642 AC: 598481 AN: 932342

Other (OTH) AF: 0.609 AC: 26117 AN: 42890

GnomAD4 genome AF: 0.533 AC: 79696 AN: 149390 Hom.: 24311 Cov.: 0 AF XY: 0.540 AC XY: 39331 AN XY: 72858

African (AFR) AF: 0.203 AC: 8169 AN: 40238

American (AMR) AF: 0.652 AC: 9794 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2364 AN: 3450

East Asian (EAS) AF: 0.739 AC: 3715 AN: 5028

South Asian (SAS) AF: 0.649 AC: 2999 AN: 4624

European-Finnish (FIN) AF: 0.643 AC: 6639 AN: 10324

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 43944 AN: 67440

Other (OTH) AF: 0.559 AC: 1160 AN: 2076

Alfa AF: 0.497 Hom.: 2701

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82

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; COSMIC: COSV63532021;