11-114266090-T-C

Variant names:

• chr11-114266090-T-C
• rs11214921
• ENST00000535401.5:c.-130+3156T>C

Variant summary

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

The NM_001372047.1(NNMT):​c.-130+3156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,036 control chromosomes in the GnomAD database, including 4,599 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 0.24 (4599 hom., cov: 31)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 3 publications found

Genes affected

NNMT (HGNC:7861): (nicotinamide N-methyltransferase) N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver. This gene encodes the protein responsible for this enzymatic activity which uses S-adenosyl methionine as the methyl donor. [provided by RefSeq, Jul 2008]

ENSG00000256947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372047.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	NM_001372047.1		c.-130+3156T>C		intron	N/A	NP_001358976.1	P40261
	NNMT	NR_164073.1		n.373+3156T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000535401.5	TSL:1	c.-130+3156T>C		intron	N/A	ENSP00000441434.1	P40261
	NNMT	ENST00000858477.1		c.-130+3156T>C		intron	N/A	ENSP00000528536.1
	NNMT	ENST00000858478.1		c.-157+3156T>C		intron	N/A	ENSP00000528537.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36694 AN: 151918 Hom.: 4595 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.242 AC: 36726 AN: 152036 Hom.: 4599 Cov.: 31 AF XY: 0.246 AC XY: 18310 AN XY: 74294

African (AFR) AF: 0.257 AC: 10642 AN: 41450

American (AMR) AF: 0.176 AC: 2690 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 625 AN: 3462

East Asian (EAS) AF: 0.403 AC: 2077 AN: 5154

South Asian (SAS) AF: 0.296 AC: 1423 AN: 4812

European-Finnish (FIN) AF: 0.314 AC: 3318 AN: 10564

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15261 AN: 67986

Other (OTH) AF: 0.227 AC: 480 AN: 2116

Alfa AF: 0.231 Hom.: 515

Bravo AF: 0.231

Asia WGS AF: 0.341 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.21
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: rs11214921; hg19: chr11-114136812;