rs2852447

Variant names:

• chr11-114308979-T-C
• rs2852447
• NM_006169.3:c.363-3066T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-114308979-T-C
• chr11-114308979-T-G

Variant summary

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

The NM_006169.3(NNMT):​c.363-3066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,036 control chromosomes in the GnomAD database, including 34,510 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 0.65 (34510 hom., cov: 31)
• Consequence: NNMT NM_006169.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006169.3. 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_006169.3	MANE Select	c.363-3066T>C		intron	N/A	NP_006160.1	P40261
	NNMT	NM_001372045.1		c.363-3066T>C		intron	N/A	NP_001358974.1	P40261
	NNMT	NM_001372046.1		c.363-3066T>C		intron	N/A	NP_001358975.1	P40261

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000299964.4	TSL:1 MANE Select	c.363-3066T>C		intron	N/A	ENSP00000299964.3	P40261
	NNMT	ENST00000535401.5	TSL:1	c.363-3066T>C		intron	N/A	ENSP00000441434.1	P40261
	NNMT	ENST00000713573.1		c.363-3066T>C		intron	N/A	ENSP00000518865.1	P40261

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98895 AN: 151918 Hom.: 34501 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.651 AC: 98932 AN: 152036 Hom.: 34510 Cov.: 31 AF XY: 0.656 AC XY: 48723 AN XY: 74328

African (AFR) AF: 0.366 AC: 15160 AN: 41436

American (AMR) AF: 0.719 AC: 10982 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2515 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4216 AN: 5144

South Asian (SAS) AF: 0.711 AC: 3423 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8439 AN: 10588

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51934 AN: 67996

Other (OTH) AF: 0.657 AC: 1387 AN: 2112

Alfa AF: 0.722 Hom.: 125825

Bravo AF: 0.636

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.52
PhyloP100		0.99
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: rs2852447; hg19: chr11-114179701;