11-114262697-C-T

Variant names:

• chr11-114262697-C-T
• rs694539
• ENST00000535401.5:c.-216-151C>T

Variant summary

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

The ENST00000535401.5(NNMT):​c.-216-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,980 control chromosomes in the GnomAD database, including 3,617 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 0.21 (3617 hom., cov: 32)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 41 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNMT	NM_001372047.1	c.-216-151C>T		intron_variant	Intron 1 of 4		NP_001358976.1
NNMT	NR_164073.1	n.287-151C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-216-151C>T		intron_variant	Intron 1 of 4	1		ENSP00000441434.1
NNMT	ENST00000535185.5	n.93-151C>T		intron_variant	Intron 1 of 2	3
ENSG00000256947	ENST00000544925.1	n.56+6787G>A		intron_variant	Intron 2 of 2	5
NNMT	ENST00000541090.1	n.-191C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32271 AN: 151860 Hom.: 3615 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.212 AC: 32290 AN: 151980 Hom.: 3617 Cov.: 32 AF XY: 0.220 AC XY: 16366 AN XY: 74306

African (AFR) AF: 0.242 AC: 10012 AN: 41390

American (AMR) AF: 0.192 AC: 2938 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1707 AN: 5154

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4822

European-Finnish (FIN) AF: 0.299 AC: 3156 AN: 10570

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11891 AN: 67972

Other (OTH) AF: 0.196 AC: 413 AN: 2108

Alfa AF: 0.188 Hom.: 11770

Bravo AF: 0.206

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		-1.2
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: rs694539; hg19: chr11-114133419;