rs2852447

Positions:

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

Variant summary

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

The ENST00000299964.4(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 ENST00000299964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_006169.3	c.363-3066T>C		intron_variant		ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.363-3066T>C		intron_variant		1	NM_006169.3	ENSP00000299964	P1
	ENST00000544925.1	n.51-39490A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.657

Alfa AF: 0.745 Hom.: 85732

Bravo AF: 0.636

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.52

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: rs2852447; hg19: chr11-114179701;