11-114258335-G-T

Variant names:

• chr11-114258335-G-T
• rs505978
• ENST00000535401.5:c.-217+457G>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+457G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,164 control chromosomes in the GnomAD database, including 7,982 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 0.32 (7982 hom., cov: 33)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	NM_001372047.1		c.-217+457G>T		intron	N/A	NP_001358976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000535401.5	TSL:1	c.-217+457G>T		intron	N/A	ENSP00000441434.1
	NNMT	ENST00000535185.5	TSL:3	n.92+457G>T		intron	N/A
	ENSG00000256947	ENST00000544925.1	TSL:5	n.56+11149C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48114 AN: 152046 Hom.: 7972 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.316 AC: 48154 AN: 152164 Hom.: 7982 Cov.: 33 AF XY: 0.324 AC XY: 24091 AN XY: 74406

African (AFR) AF: 0.290 AC: 12031 AN: 41522

American (AMR) AF: 0.297 AC: 4543 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2850 AN: 5150

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4824

European-Finnish (FIN) AF: 0.433 AC: 4589 AN: 10608

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20365 AN: 67982

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.298 Hom.: 25752

Bravo AF: 0.304

Asia WGS AF: 0.499 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.49
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs505978; hg19: chr11-114129057;