rs2113509

Variant names:

• chr2-151287683-G-A
• rs2113509
• NM_004688.3:c.-7+1910C>T

Variant summary

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

The NM_004688.3(NMI):​c.-7+1910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,804 control chromosomes in the GnomAD database, including 6,953 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 0.23 (6953 hom., cov: 32)
• Consequence: NMI NM_004688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMI	NM_004688.3	c.-7+1910C>T		intron_variant	Intron 1 of 7	ENST00000243346.10	NP_004679.2
NMI	XM_005246941.3	c.-7+1208C>T		intron_variant	Intron 1 of 7		XP_005246998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMI	ENST00000243346.10	c.-7+1910C>T		intron_variant	Intron 1 of 7	1	NM_004688.3	ENSP00000243346.5
NMI	ENST00000414946.1	c.-7+1208C>T		intron_variant	Intron 2 of 3	5		ENSP00000387373.1
NMI	ENST00000477072.1	n.271+1910C>T		intron_variant	Intron 1 of 1	3
NMI	ENST00000491771.5	n.271+1910C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35588 AN: 151686 Hom.: 6934 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.235 AC: 35651 AN: 151804 Hom.: 6953 Cov.: 32 AF XY: 0.229 AC XY: 16978 AN XY: 74186

African (AFR) AF: 0.534 AC: 22082 AN: 41354

American (AMR) AF: 0.158 AC: 2410 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.0686 AC: 354 AN: 5158

South Asian (SAS) AF: 0.183 AC: 880 AN: 4808

European-Finnish (FIN) AF: 0.0580 AC: 609 AN: 10504

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8185 AN: 67964

Other (OTH) AF: 0.209 AC: 441 AN: 2106

Alfa AF: 0.151 Hom.: 1442

Bravo AF: 0.254

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		0.27
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: rs2113509; hg19: chr2-152144197;