1-209432291-TAGCAGCAGCAGCAGCAGCAGCAGCAGC-TAGCAGCAGCAGC

Variant names:

• chr1-209432291-TAGCAGCAGCAGCAGC-T
• rs3842530
• ENST00000366437.8:n.665_679delGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000366437.8(MIR205HG):​n.665_679delGCAGCAGCAGCAGCA 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 0.00197 in 1,309,566 control chromosomes in the GnomAD database, including 34 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 0.0014 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (32 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.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00136 (204/149532) while in subpopulation SAS AF = 0.0296 (137/4628). AF 95% confidence interval is 0.0256. There are 2 homozygotes in GnomAd4. There are 136 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• 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.611_625delGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 3 of 3
MIR205HG	NR_145434.1	n.746_760delGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5
MIR205HG	NR_145435.1	n.694_708delGCAGCAGCAGCAGCA		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.665_679delGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3
MIR205HG	ENST00000429156.7	n.776_790delGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 5 of 5	3
MIR205HG	ENST00000431096.7	n.697_711delGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 207 AN: 149422 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000333

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00297

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0000970

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.000486

GnomAD2 exomes AF: 0.00509 AC: 991 AN: 194576 AF XY: 0.00619

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.00628

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.00205 AC: 2377 AN: 1160034 Hom.: 32 AF XY: 0.00281 AC XY: 1610 AN XY: 573554

African (AFR) AF: 0.000889 AC: 23 AN: 25868

American (AMR) AF: 0.000907 AC: 30 AN: 33082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15758

East Asian (EAS) AF: 0.00463 AC: 74 AN: 15982

South Asian (SAS) AF: 0.0233 AC: 1857 AN: 79546

European-Finnish (FIN) AF: 0.000851 AC: 25 AN: 29380

Middle Eastern (MID) AF: 0.00538 AC: 22 AN: 4088

European-Non Finnish (NFE) AF: 0.000257 AC: 235 AN: 914232

Other (OTH) AF: 0.00264 AC: 111 AN: 42098

GnomAD4 genome AF: 0.00136 AC: 204 AN: 149532 Hom.: 2 Cov.: 0 AF XY: 0.00186 AC XY: 136 AN XY: 72946

African (AFR) AF: 0.000770 AC: 31 AN: 40278

American (AMR) AF: 0.000332 AC: 5 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00298 AC: 15 AN: 5032

South Asian (SAS) AF: 0.0296 AC: 137 AN: 4628

European-Finnish (FIN) AF: 0.0000970 AC: 1 AN: 10314

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000193 AC: 13 AN: 67510

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.0117 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; COSMIC: COSV63532511;