chr1-209432291-TAGC-T

Variant names:

• chr1-209432291-TAGC-T
• rs3842530
• ENST00000366437.8:n.677_679delGCA

Variant summary

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

The ENST00000366437.8(MIR205HG):​n.677_679delGCA 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 0.00339 in 1,329,502 control chromosomes in the GnomAD database, including 68 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (42 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (26 hom.)
• Consequence: MIR205HG ENST00000366437.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749
• 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 afr. GnomAd4 allele frequency = 0.0132 (1976/149556) while in subpopulation AFR AF = 0.0449 (1806/40258). AF 95% confidence interval is 0.0431. There are 42 homozygotes in GnomAd4. There are 937 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366437.8. 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
	MIR205HG	NR_145433.1		n.623_625delGCA		non_coding_transcript_exon	Exon 3 of 3
	MIR205HG	NR_145434.1		n.758_760delGCA		non_coding_transcript_exon	Exon 5 of 5
	MIR205HG	NR_145435.1		n.706_708delGCA		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR205HG	ENST00000366437.8	TSL:3	n.677_679delGCA		non_coding_transcript_exon	Exon 4 of 4
	MIR205HG	ENST00000429156.7	TSL:3	n.788_790delGCA		non_coding_transcript_exon	Exon 5 of 5
	MIR205HG	ENST00000431096.7	TSL:3	n.709_711delGCA		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1972 AN: 149446 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.000793

Gnomad SAS AF: 0.00151

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000874

Gnomad OTH AF: 0.0107

GnomAD2 exomes AF: 0.00397 AC: 772 AN: 194576 AF XY: 0.00352

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.00274

Gnomad EAS exome AF: 0.00176

Gnomad FIN exome AF: 0.000985

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00214 AC: 2529 AN: 1179946 Hom.: 26 AF XY: 0.00211 AC XY: 1230 AN XY: 583424

African (AFR) AF: 0.0464 AC: 1193 AN: 25718

American (AMR) AF: 0.00242 AC: 82 AN: 33942

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 46 AN: 16238

East Asian (EAS) AF: 0.00141 AC: 23 AN: 16336

South Asian (SAS) AF: 0.00235 AC: 190 AN: 80886

European-Finnish (FIN) AF: 0.000669 AC: 20 AN: 29898

Middle Eastern (MID) AF: 0.00241 AC: 10 AN: 4144

European-Non Finnish (NFE) AF: 0.000852 AC: 792 AN: 930016

Other (OTH) AF: 0.00405 AC: 173 AN: 42768

GnomAD4 genome AF: 0.0132 AC: 1976 AN: 149556 Hom.: 42 Cov.: 0 AF XY: 0.0128 AC XY: 937 AN XY: 72958

African (AFR) AF: 0.0449 AC: 1806 AN: 40258

American (AMR) AF: 0.00459 AC: 69 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 6 AN: 3456

East Asian (EAS) AF: 0.000795 AC: 4 AN: 5034

South Asian (SAS) AF: 0.00151 AC: 7 AN: 4628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10332

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000874 AC: 59 AN: 67530

Other (OTH) AF: 0.0106 AC: 22 AN: 2080

Alfa AF: 0.00302 Hom.: 2701

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.75

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: COSV63532607;