rs61768480

Variant names:

• chr1-1167770-G-A
• rs61768480
• XR_007065348.1:n.4518G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007065348.1(LOC124903818):​n.4518G>A 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 0.237 in 464,264 control chromosomes in the GnomAD database, including 14,569 homozygotes. 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 0.23 (4562 hom., cov: 33)
  • Exomes 𝑓: 0.24 (10007 hom.)
• Consequence: LOC124903818 XR_007065348.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

Genes affected

LOC124903818 (HGNC:):

MIR200A (HGNC:31578): (microRNA 200a) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903818	XR_007065348.1	n.4518G>A		non_coding_transcript_exon_variant	Exon 2 of 2
MIR200A	NR_029834.1	n.-93G>A		upstream_gene_variant
MIR200A	unassigned_transcript_10	n.-146G>A		upstream_gene_variant
MIR200A	unassigned_transcript_9	n.-108G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR200A	ENST00000384875.3	n.-93G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34991 AN: 151970 Hom.: 4561 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.241 AC: 75091 AN: 312176 Hom.: 10007 AF XY: 0.239 AC XY: 42282 AN XY: 176630

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0286

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.230 AC: 35011 AN: 152088 Hom.: 4562 Cov.: 33 AF XY: 0.230 AC XY: 17119 AN XY: 74352

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0308

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.219

Alfa AF: 0.262 Hom.: 686

Bravo AF: 0.211

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61768480; hg19: chr1-1103150;