1-209432291-TAGCAGCAGCAGCAGCAGCAGCAGCAGC-TAGCAGCAGCAGCAGCAGCAGCAGC

Position:

• chr1-209432291-TAGCAGCAGCAGCAGCAGCAGCAGCAGC-TAGCAGCAGCAGCAGCAGCAGCAGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000433108.1(MIR205HG):​n.3132_3134delGCA 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 ENST00000433108.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR205HG	NR_145433.1	n.623_625delGCA		non_coding_transcript_exon_variant	3/3
MIR205HG	NR_145434.1	n.758_760delGCA		non_coding_transcript_exon_variant	5/5
MIR205HG	NR_145435.1	n.706_708delGCA		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR205HG	ENST00000366437.7	n.484_486delGCA		non_coding_transcript_exon_variant	4/4	3
MIR205HG	ENST00000429156.6	n.785_787delGCA		non_coding_transcript_exon_variant	5/5	3
MIR205HG	ENST00000431096.6	n.706_708delGCA		non_coding_transcript_exon_variant	4/4	3

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

GnomAD3 exomes AF: 0.00397 AC: 772 AN: 194576 Hom.: 16 AF XY: 0.00352 AC XY: 371 AN XY: 105446

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 SAS exome AF: 0.00261

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

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.00283

Gnomad4 EAS exome AF: 0.00141

Gnomad4 SAS exome AF: 0.00235

Gnomad4 FIN exome AF: 0.000669

Gnomad4 NFE exome AF: 0.000852

Gnomad4 OTH exome AF: 0.00405

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

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.00459

Gnomad4 ASJ AF: 0.00174

Gnomad4 EAS AF: 0.000795

Gnomad4 SAS AF: 0.00151

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000874

Gnomad4 OTH AF: 0.0106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3842530; hg19: chr1-209605636;