rs2504172

Variant names:

• chrX-147260534-T-C
• rs2504172
• ENST00000385265.1:n.92A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-147260534-T-C
• chrX-147260534-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000385265.1(MIR509-1):​n.92A>G variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 112,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 17 hem.)
  • Failed GnomAD Quality Control
• Consequence: MIR509-1 ENST00000385265.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 0 publications found

Genes affected

MIR509-1 (HGNC:32146): (microRNA 509-1) 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]

ENSG00000284377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR509-1	NR_030236.1	n.92A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1
LOC105373347	XR_005647083.2	n.208-8475T>C		intron_variant	Intron 2 of 3
LOC105373347	XR_005647084.2	n.158-8475T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR509-1	ENST00000385265.1	n.92A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000284377	ENST00000639829.1	n.412-8475T>C		intron_variant	Intron 3 of 4	5
ENSG00000284377	ENST00000701574.2	n.209-8475T>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 20 AN: 111953 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000565

Gnomad SAS AF: 0.000377

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 27 AN: 182666 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000763

Gnomad AMR exome AF: 0.000475

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000139 AC: 38 AN: 273362 Hom.: 0 Cov.: 0 AF XY: 0.000156 AC XY: 17 AN XY: 108774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 1 AN: 8365

American (AMR) AF: 0.000487 AC: 14 AN: 28722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8717

East Asian (EAS) AF: 0.000308 AC: 3 AN: 9756

South Asian (SAS) AF: 0.000325 AC: 13 AN: 39939

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24329

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2104

European-Non Finnish (NFE) AF: 0.0000431 AC: 6 AN: 139095

Other (OTH) AF: 0.0000811 AC: 1 AN: 12335

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000303679), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000179 AC: 20 AN: 112006 Hom.: 0 Cov.: 23 AF XY: 0.0000877 AC XY: 3 AN XY: 34194

African (AFR) AF: 0.0000973 AC: 3 AN: 30836

American (AMR) AF: 0.000189 AC: 2 AN: 10596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.000567 AC: 2 AN: 3528

South Asian (SAS) AF: 0.000378 AC: 1 AN: 2645

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000226 AC: 12 AN: 53134

Other (OTH) AF: 0.00 AC: 0 AN: 1525

Alfa AF: 0.0000868 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.80
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs2504172; hg19: chrX-146342052; COSMIC: COSV66116265;