11-114266090-T-C

Variant names:

• chr11-114266090-T-C
• rs11214921
• ENST00000535401.5:c.-130+3156T>C

Variant summary

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

The NM_001372047.1(NNMT):​c.-130+3156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,036 control chromosomes in the GnomAD database, including 4,599 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 0.24 (4599 hom., cov: 31)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNMT	NM_001372047.1	c.-130+3156T>C		intron_variant	Intron 2 of 4		NP_001358976.1
NNMT	NR_164073.1	n.373+3156T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-130+3156T>C		intron_variant	Intron 2 of 4	1		ENSP00000441434.1
NNMT	ENST00000535185.5	n.179+3156T>C		intron_variant	Intron 2 of 2	3
NNMT	ENST00000541090.1	n.47+3156T>C		intron_variant	Intron 1 of 2	3
ENSG00000256947	ENST00000544925.1	n.56+3394A>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36694 AN: 151918 Hom.: 4595 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.242 AC: 36726 AN: 152036 Hom.: 4599 Cov.: 31 AF XY: 0.246 AC XY: 18310 AN XY: 74294

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.227

Alfa AF: 0.231 Hom.: 515

Bravo AF: 0.231

Asia WGS AF: 0.341 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.70

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: rs11214921; hg19: chr11-114136812;