11-114293282-A-G

Position:

• chr11-114293282-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372047.1(NNMT):​c.-129-3146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,872 control chromosomes in the GnomAD database, including 31,274 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 0.62 (31274 hom., cov: 30)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_001372047.1	c.-129-3146A>G		intron_variant			NP_001358976.1
NNMT	NR_164073.1	n.374-4669A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-129-3146A>G		intron_variant		1		ENSP00000441434.1
NNMT	ENST00000541090.1	n.188-18763A>G		intron_variant		3
ENSG00000256947	ENST00000544925.1	n.51-23793T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94496 AN: 151752 Hom.: 31271 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.622 AC: 94522 AN: 151872 Hom.: 31274 Cov.: 30 AF XY: 0.618 AC XY: 45868 AN XY: 74204

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.652

Alfa AF: 0.715 Hom.: 40107

Bravo AF: 0.623

Asia WGS AF: 0.565 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs2852432; hg19: chr11-114164004;