11-114258423-C-T

Variant names:

• chr11-114258423-C-T
• rs683271
• ENST00000535401.5:c.-217+545C>T

Variant summary

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

The NM_001372047.1(NNMT):​c.-217+545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,156 control chromosomes in the GnomAD database, including 7,064 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 0.29 (7064 hom., cov: 33)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.-217+545C>T		intron	N/A	NP_001358976.1	P40261

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000535401.5	TSL:1	c.-217+545C>T		intron	N/A	ENSP00000441434.1	P40261
	NNMT	ENST00000858477.1		c.-352+545C>T		intron	N/A	ENSP00000528536.1
	NNMT	ENST00000858478.1		c.-244+545C>T		intron	N/A	ENSP00000528537.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44411 AN: 152038 Hom.: 7051 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.292 AC: 44447 AN: 152156 Hom.: 7064 Cov.: 33 AF XY: 0.300 AC XY: 22339 AN XY: 74378

African (AFR) AF: 0.205 AC: 8509 AN: 41534

American (AMR) AF: 0.290 AC: 4438 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2842 AN: 5134

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4828

European-Finnish (FIN) AF: 0.434 AC: 4592 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20337 AN: 67984

Other (OTH) AF: 0.268 AC: 568 AN: 2116

Alfa AF: 0.269 Hom.: 2222

Bravo AF: 0.276

Asia WGS AF: 0.491 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.53
PhyloP100		-0.61
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: rs683271; hg19: chr11-114129145;