11-114258423-C-T

Variant names:

• chr11-114258423-C-T
• rs683271
• ENST00000535401.5:c.-217+545C>T

Variant summary

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

The NM_001372047.1(NNMT):​c.-217+545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,156 control chromosomes in the GnomAD database, including 7,064 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 0.29 (7064 hom., cov: 33)
• Consequence: NNMT NM_001372047.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NNMT	NM_001372047.1	c.-217+545C>T		intron_variant	Intron 1 of 4		NP_001358976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-217+545C>T		intron_variant	Intron 1 of 4	1		ENSP00000441434.1
NNMT	ENST00000535185.5	n.92+545C>T		intron_variant	Intron 1 of 2	3
ENSG00000256947	ENST00000544925.1	n.56+11061G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44411 AN: 152038 Hom.: 7051 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.292 AC: 44447 AN: 152156 Hom.: 7064 Cov.: 33 AF XY: 0.300 AC XY: 22339 AN XY: 74378

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.268

Alfa AF: 0.224 Hom.: 886

Bravo AF: 0.276

Asia WGS AF: 0.491 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.53

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: rs683271; hg19: chr11-114129145;