rs577948

Variant names:

• chr11-122159482-A-G
• rs577948
• ENST00000534782.4:n.387+20854T>C

Variant summary

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

The ENST00000534782.4(MIR100HG):​n.387+20854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,092 control chromosomes in the GnomAD database, including 9,506 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 0.34 (9506 hom., cov: 32)
• Consequence: MIR100HG ENST00000534782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_024430.2	n.410-3850T>C		intron_variant	Intron 2 of 3
MIR100HG	NR_137179.1	n.364-3850T>C		intron_variant	Intron 3 of 4
MIR100HG	NR_137180.1	n.422-3850T>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000534782.4	n.387+20854T>C		intron_variant	Intron 2 of 2	1
MIR100HG	ENST00000532350.6	n.388-3850T>C		intron_variant	Intron 2 of 2	5
MIR100HG	ENST00000533109.6	n.917-3850T>C		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51507 AN: 151974 Hom.: 9498 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.339 AC: 51525 AN: 152092 Hom.: 9506 Cov.: 32 AF XY: 0.343 AC XY: 25497 AN XY: 74324

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.373

Alfa AF: 0.394 Hom.: 26169

Bravo AF: 0.328

Asia WGS AF: 0.473 AC: 1644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs577948; hg19: chr11-122030190;