chr2-151279000-A-G

Position:

• chr2-151279000-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004688.3(NMI):​c.178-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,543,842 control chromosomes in the GnomAD database, including 17,070 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 0.19 (3768 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13302 hom.)
• Consequence: NMI NM_004688.3 intron
• Scores: Splicing: ADA: 0.004861
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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]

NMI (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMI	NM_004688.3	c.178-10T>C		intron_variant		ENST00000243346.10	NP_004679.2
NMI	XM_047446270.1	c.451-10T>C		intron_variant			XP_047302226.1
NMI	XM_005246941.3	c.178-10T>C		intron_variant			XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.178-10T>C		intron_variant		1	NM_004688.3	ENSP00000243346.5
NMI	ENST00000491771.5	n.359-10T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28868 AN: 152050 Hom.: 3763 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.137 AC: 32045 AN: 233598 Hom.: 2916 AF XY: 0.138 AC XY: 17421 AN XY: 126170

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.0852

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.127 AC: 176519 AN: 1391674 Hom.: 13302 Cov.: 23 AF XY: 0.129 AC XY: 89325 AN XY: 690870

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.0893

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.0635

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.190 AC: 28908 AN: 152168 Hom.: 3768 Cov.: 32 AF XY: 0.186 AC XY: 13820 AN XY: 74406

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.179

Alfa AF: 0.151 Hom.: 606

Bravo AF: 0.200

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0049
dbscSNV1_RF	Benign	0.23
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: rs289831; hg19: chr2-152135514; COSMIC: COSV54638308; COSMIC: COSV54638308;