rs11730

Positions:

• chr2-151270497-A-G

Variant summary

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

The NM_004688.3(NMI):​c.*196T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 563,072 control chromosomes in the GnomAD database, including 52,132 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 0.36 (12074 hom., cov: 33)
  • Exomes 𝑓: 0.43 (40058 hom.)
• Consequence: NMI NM_004688.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

Genes affected

NMI (HGNC:7854): (N-myc and STAT interactor) NMYC interactor (NMI) encodes a protein that interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. The NMI protein also interacts with all STATs except STAT2 and augments STAT-mediated transcription in response to cytokines IL2 and IFN-gamma. The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMI	NM_004688.3	c.*196T>C		3_prime_UTR_variant	8/8	ENST00000243346.10	NP_004679.2
NMI	XM_005246941.3	c.*196T>C		3_prime_UTR_variant	8/8		XP_005246998.1
NMI	XM_047446270.1	c.*196T>C		3_prime_UTR_variant	8/8		XP_047302226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.*196T>C		3_prime_UTR_variant	8/8	1	NM_004688.3	ENSP00000243346	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54990 AN: 152064 Hom.: 12063 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.432 AC: 177523 AN: 410890 Hom.: 40058 Cov.: 4 AF XY: 0.426 AC XY: 92294 AN XY: 216726

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.361 AC: 54997 AN: 152182 Hom.: 12074 Cov.: 33 AF XY: 0.368 AC XY: 27379 AN XY: 74398

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.357

Alfa AF: 0.432 Hom.: 14430

Bravo AF: 0.349

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11730; hg19: chr2-152127011;