rs394884

Variant names:

• chr2-151272246-C-T
• rs394884
• NM_004688.3:c.635-514G>A

Variant summary

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

The NM_004688.3(NMI):​c.635-514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,086 control chromosomes in the GnomAD database, including 7,712 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 0.26 (7712 hom., cov: 33)
• Consequence: NMI NM_004688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.635-514G>A		intron_variant	Intron 6 of 7	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.908-514G>A		intron_variant	Intron 6 of 7		XP_047302226.1
NMI	XM_005246941.3	c.635-514G>A		intron_variant	Intron 6 of 7		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.635-514G>A		intron_variant	Intron 6 of 7	1	NM_004688.3	ENSP00000243346.5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39516 AN: 151968 Hom.: 7692 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.260 AC: 39589 AN: 152086 Hom.: 7712 Cov.: 33 AF XY: 0.254 AC XY: 18871 AN XY: 74364

African (AFR) AF: 0.555 AC: 23014 AN: 41438

American (AMR) AF: 0.178 AC: 2714 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3468

East Asian (EAS) AF: 0.128 AC: 662 AN: 5182

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4824

European-Finnish (FIN) AF: 0.0770 AC: 816 AN: 10592

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9987 AN: 67980

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.205 Hom.: 630

Bravo AF: 0.278

Asia WGS AF: 0.216 AC: 750 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.79
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs394884; hg19: chr2-152128760;