11-122214427-A-G

Variant names:

• chr11-122214427-A-G
• rs11218553
• ENST00000527474.5:n.899-34029T>C

Variant summary

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

The ENST00000527474.5(MIR100HG):​n.899-34029T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,140 control chromosomes in the GnomAD database, including 2,691 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 0.18 (2691 hom., cov: 32)
• Consequence: MIR100HG ENST00000527474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_137179.1	n.301-34029T>C		intron_variant	Intron 2 of 4
MIR100HG	NR_137180.1	n.359-34029T>C		intron_variant	Intron 2 of 4
MIR100HG	NR_137192.1	n.614-34029T>C		intron_variant	Intron 2 of 3
MIR100HG	NR_137193.1	n.359-34029T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000527474.5	n.899-34029T>C		intron_variant	Intron 3 of 3	1
MIR100HG	ENST00000529733.5	n.498-10832T>C		intron_variant	Intron 2 of 2	4
MIR100HG	ENST00000533109.6	n.854-34029T>C		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 152024 Hom.: 2693 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.182 AC: 27708 AN: 152140 Hom.: 2691 Cov.: 32 AF XY: 0.184 AC XY: 13673 AN XY: 74376

African (AFR) AF: 0.143 AC: 5941 AN: 41516

American (AMR) AF: 0.220 AC: 3358 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5170

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4812

European-Finnish (FIN) AF: 0.139 AC: 1473 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12545 AN: 67994

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.184 Hom.: 5190

Bravo AF: 0.184

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.6
DANN	Benign	0.71
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs11218553; hg19: chr11-122085135;