rs657514

Variant names:

• chr11-122174496-C-A
• rs657514
• ENST00000534782.4:n.387+5840G>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+5840G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,824 control chromosomes in the GnomAD database, including 21,547 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 0.53 (21547 hom., cov: 32)
• Consequence: MIR100HG ENST00000534782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_024430.2	n.409+5840G>T		intron_variant	Intron 2 of 3
MIR100HG	NR_137179.1	n.363+5840G>T		intron_variant	Intron 3 of 4
MIR100HG	NR_137180.1	n.421+5840G>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000534782.4	n.387+5840G>T		intron_variant	Intron 2 of 2	1
MIR100HG	ENST00000654571.2	n.1470G>T		non_coding_transcript_exon_variant	Exon 5 of 5
MIR100HG	ENST00000660329.3	n.939G>T		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80719 AN: 151706 Hom.: 21525 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.532 AC: 80778 AN: 151824 Hom.: 21547 Cov.: 32 AF XY: 0.533 AC XY: 39570 AN XY: 74180

African (AFR) AF: 0.578 AC: 23924 AN: 41424

American (AMR) AF: 0.536 AC: 8185 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3472

East Asian (EAS) AF: 0.581 AC: 2985 AN: 5138

South Asian (SAS) AF: 0.474 AC: 2271 AN: 4796

European-Finnish (FIN) AF: 0.536 AC: 5633 AN: 10518

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34116 AN: 67908

Other (OTH) AF: 0.543 AC: 1142 AN: 2102

Alfa AF: 0.537 Hom.: 9427

Bravo AF: 0.539

Asia WGS AF: 0.580 AC: 2013 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs657514; hg19: chr11-122045204;