chr11-114288721-T-C

Position:

• chr11-114288721-T-C

Variant summary

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

The ENST00000535401.5(NNMT):​c.-129-7707T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,046 control chromosomes in the GnomAD database, including 7,144 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 0.30 (7144 hom., cov: 32)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNMT	NM_001372047.1	c.-129-7707T>C		intron_variant
NNMT	NR_164073.1	n.374-9230T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NNMT	ENST00000535401.5	c.-129-7707T>C		intron_variant		1		P1
	ENST00000544925.1	n.51-19232A>G		intron_variant, non_coding_transcript_variant		5
NNMT	ENST00000541090.1	n.187+18264T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45619 AN: 151928 Hom.: 7137 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.300 AC: 45646 AN: 152046 Hom.: 7144 Cov.: 32 AF XY: 0.305 AC XY: 22661 AN XY: 74332

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.278

Alfa AF: 0.291 Hom.: 863

Bravo AF: 0.286

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.78

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: rs10400393; hg19: chr11-114159443;