rs4646335

Variant names:

• chr11-114296220-A-T
• rs4646335
• ENST00000535401.5:c.-129-208A>T

Variant summary

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

The ENST00000535401.5(NNMT):​c.-129-208A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 203,204 control chromosomes in the GnomAD database, including 4,393 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 0.17 (2893 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1500 hom.)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNMT	NM_006169.3	c.-337A>T		upstream_gene_variant		ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.-337A>T		upstream_gene_variant		1	NM_006169.3	ENSP00000299964.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26115 AN: 151862 Hom.: 2890 Cov.: 31

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.219 AC: 11239 AN: 51224 Hom.: 1500 Cov.: 0 AF XY: 0.221 AC XY: 5781 AN XY: 26212

African (AFR) AF: 0.0423 AC: 100 AN: 2366

American (AMR) AF: 0.244 AC: 782 AN: 3210

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 416 AN: 1978

East Asian (EAS) AF: 0.449 AC: 1891 AN: 4210

South Asian (SAS) AF: 0.248 AC: 459 AN: 1850

European-Finnish (FIN) AF: 0.269 AC: 476 AN: 1768

Middle Eastern (MID) AF: 0.151 AC: 35 AN: 232

European-Non Finnish (NFE) AF: 0.199 AC: 6444 AN: 32386

Other (OTH) AF: 0.197 AC: 636 AN: 3224

GnomAD4 genome AF: 0.172 AC: 26120 AN: 151980 Hom.: 2893 Cov.: 31 AF XY: 0.178 AC XY: 13249 AN XY: 74278

African (AFR) AF: 0.0448 AC: 1859 AN: 41482

American (AMR) AF: 0.194 AC: 2964 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2056 AN: 5134

South Asian (SAS) AF: 0.243 AC: 1169 AN: 4806

European-Finnish (FIN) AF: 0.285 AC: 3003 AN: 10554

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13749 AN: 67958

Other (OTH) AF: 0.150 AC: 315 AN: 2106

Alfa AF: 0.205 Hom.: 1989

Bravo AF: 0.162

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		0.47
PromoterAI		-0.011	Neutral
Mutation Taster		=300/0	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: rs4646335; hg19: chr11-114166942;