rs3854012

Variant names:

• chr2-151280592-C-T
• rs3854012
• NM_004688.3:c.177+1356G>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.177+1356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,032 control chromosomes in the GnomAD database, including 14,967 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 0.44 (14967 hom., cov: 32)
• Consequence: NMI NM_004688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.177+1356G>A		intron_variant	Intron 3 of 7	ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.450+1356G>A		intron_variant	Intron 3 of 7		XP_047302226.1
NMI	XM_005246941.3	c.177+1356G>A		intron_variant	Intron 3 of 7		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.177+1356G>A		intron_variant	Intron 3 of 7	1	NM_004688.3	ENSP00000243346.5
NMI	ENST00000491771.5	n.359-1602G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66674 AN: 151914 Hom.: 14948 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.439 AC: 66726 AN: 152032 Hom.: 14967 Cov.: 32 AF XY: 0.443 AC XY: 32909 AN XY: 74306

African (AFR) AF: 0.378 AC: 15696 AN: 41484

American (AMR) AF: 0.536 AC: 8185 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1962 AN: 5148

South Asian (SAS) AF: 0.328 AC: 1583 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5709 AN: 10562

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31065 AN: 67952

Other (OTH) AF: 0.410 AC: 866 AN: 2112

Alfa AF: 0.453 Hom.: 1999

Bravo AF: 0.440

Asia WGS AF: 0.332 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.85
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: rs3854012; hg19: chr2-152137106;