rs629367

Variant names:

• chr11-122146306-C-A
• rs629367
• ENST00000534782.4:n.387+34030G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-122146306-C-A
• chr11-122146306-C-G
• chr11-122146306-C-T

Variant summary

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

The ENST00000534782.4(MIR100HG):​n.387+34030G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,176 control chromosomes in the GnomAD database, including 58,183 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 0.87 (58183 hom., cov: 32)
• Consequence: MIR100HG ENST00000534782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 29 publications found

Genes affected

MIR100HG (HGNC:39522): (mir-100-let-7a-2-mir-125b-1 cluster host gene) This gene produces long non-coding RNAs that act as regulators of cell proliferation. Alternative promoter usage and splicing results in multiple transcript variants. Some transcript variants may promote growth, while others may act to negatively regulate cell division. [provided by RefSeq, May 2016]

MIRLET7A2 (HGNC:31477): (microRNA let-7a-2) 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_024430.2	n.491+9245G>T		intron_variant	Intron 3 of 3
MIR100HG	NR_137179.1	n.445+9245G>T		intron_variant	Intron 4 of 4
MIR100HG	NR_137180.1	n.503+9245G>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000534782.4	n.387+34030G>T		intron_variant	Intron 2 of 2	1
MIR100HG	ENST00000780512.1	n.302G>T		non_coding_transcript_exon_variant	Exon 1 of 1
MIR100HG	ENST00000534297.2	n.185+9245G>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132806 AN: 152058 Hom.: 58123 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.874 AC: 132932 AN: 152176 Hom.: 58183 Cov.: 32 AF XY: 0.871 AC XY: 64841 AN XY: 74406

African (AFR) AF: 0.923 AC: 38292 AN: 41506

American (AMR) AF: 0.870 AC: 13286 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3076 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3968 AN: 5172

South Asian (SAS) AF: 0.821 AC: 3955 AN: 4820

European-Finnish (FIN) AF: 0.858 AC: 9091 AN: 10592

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58349 AN: 68022

Other (OTH) AF: 0.871 AC: 1839 AN: 2112

Alfa AF: 0.870 Hom.: 20462

Bravo AF: 0.876

Asia WGS AF: 0.803 AC: 2790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.47
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs629367; hg19: chr11-122017014; COSMIC: COSV62996667;