chr2-151282008-T-C

Position:

• chr2-151282008-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004688.3(NMI):​c.117A>G​(p.Gln39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,530,844 control chromosomes in the GnomAD database, including 256,080 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 0.60 (27219 hom., cov: 32)
  • Exomes 𝑓: 0.57 (228861 hom.)
• Consequence: NMI NM_004688.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMI	NM_004688.3	c.117A>G	p.Gln39=	synonymous_variant	3/8	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.390A>G	p.Gln130=	synonymous_variant	3/8		XP_047302226.1
NMI	XM_005246941.3	c.117A>G	p.Gln39=	synonymous_variant	3/8		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.117A>G	p.Gln39=	synonymous_variant	3/8	1	NM_004688.3	ENSP00000243346	P1
NMI	ENST00000491771.5	n.358+860A>G		intron_variant, non_coding_transcript_variant		2
NMI	ENST00000414946.1			downstream_gene_variant		5		ENSP00000387373

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90442 AN: 151872 Hom.: 27189 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.572

GnomAD3 exomes AF: 0.572 AC: 140373 AN: 245298 Hom.: 41007 AF XY: 0.563 AC XY: 74638 AN XY: 132514

Gnomad AFR exome AF: 0.641

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.439

Gnomad SAS exome AF: 0.502

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.573 AC: 789724 AN: 1378854 Hom.: 228861 Cov.: 23 AF XY: 0.570 AC XY: 393136 AN XY: 690222

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.596 AC: 90511 AN: 151990 Hom.: 27219 Cov.: 32 AF XY: 0.596 AC XY: 44269 AN XY: 74274

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.565

Alfa AF: 0.567 Hom.: 55389

Bravo AF: 0.602

Asia WGS AF: 0.468 AC: 1629 AN: 3472

EpiCase AF: 0.556

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3771886; hg19: chr2-152138522;