rs10891641

Positions:

• chr11-114268359-G-A
• chr11-114268359-G-C

Variant summary

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

The ENST00000535401.5(NNMT):​c.-130+5425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,014 control chromosomes in the GnomAD database, including 9,917 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 0.33 (9917 hom., cov: 32)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_001372047.1	c.-130+5425G>A		intron_variant			NP_001358976.1
NNMT	NR_164073.1	n.373+5425G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-130+5425G>A		intron_variant		1		ENSP00000441434	P1
	ENST00000544925.1	n.56+1125C>T		intron_variant, non_coding_transcript_variant		5
NNMT	ENST00000535185.5	n.180-1959G>A		intron_variant, non_coding_transcript_variant		3
NNMT	ENST00000541090.1	n.48-1959G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50301 AN: 151896 Hom.: 9884 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.331 AC: 50386 AN: 152014 Hom.: 9917 Cov.: 32 AF XY: 0.335 AC XY: 24876 AN XY: 74298

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.296

Alfa AF: 0.259 Hom.: 1390

Bravo AF: 0.332

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.57

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: rs10891641; hg19: chr11-114139081;