1-1168162-T-C

Variant names:

• chr1-1168162-T-C
• rs7518873
• XR_007065348.1:n.4910T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007065348.1(MIR200BHG):​n.4910T>C 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 0.875 in 151,428 control chromosomes in the GnomAD database, including 58,606 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 0.88 (58606 hom., cov: 32)
• Consequence: MIR200BHG XR_007065348.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• Publications: 3 publications found

Genes affected

MIR200BHG (HGNC:58145):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR200BHG	XR_007065348.1	n.4910T>C		non_coding_transcript_exon_variant	Exon 2 of 2
MIR200A	NR_029834.1	n.*210T>C		downstream_gene_variant
MIR200A	unassigned_transcript_10	n.*225T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR200A	ENST00000384875.3	n.*210T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132458 AN: 151310 Hom.: 58561 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.942

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.865

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.875 AC: 132558 AN: 151428 Hom.: 58606 Cov.: 32 AF XY: 0.871 AC XY: 64467 AN XY: 73982

African (AFR) AF: 0.821 AC: 33811 AN: 41194

American (AMR) AF: 0.818 AC: 12475 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3030 AN: 3464

East Asian (EAS) AF: 0.545 AC: 2754 AN: 5054

South Asian (SAS) AF: 0.872 AC: 4180 AN: 4792

European-Finnish (FIN) AF: 0.922 AC: 9753 AN: 10582

Middle Eastern (MID) AF: 0.934 AC: 271 AN: 290

European-Non Finnish (NFE) AF: 0.938 AC: 63566 AN: 67788

Other (OTH) AF: 0.865 AC: 1815 AN: 2098

Alfa AF: 0.898 Hom.: 7593

Bravo AF: 0.861

Asia WGS AF: 0.612 AC: 1595 AN: 2602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.20
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs7518873; hg19: chr1-1103542;