2-137964027-C-T

Position:

• chr2-137964027-C-T

Variant summary

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

The ENST00000410115(HNMT):​c.-141C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,432 control chromosomes in the GnomAD database, including 25,857 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 0.58 (25804 hom., cov: 33)
  • Exomes 𝑓: 0.53 (53 hom.)
• Consequence: HNMT ENST00000410115 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

Genes affected

HNMT (HGNC:5028): (histamine N-methyltransferase) In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.137964027C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNMT	ENST00000410115	c.-141C>T		5_prime_UTR_variant	1/7	5		ENSP00000386940.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88261 AN: 151928 Hom.: 25787 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.528 AC: 204 AN: 386 Hom.: 53 Cov.: 0 AF XY: 0.540 AC XY: 109 AN XY: 202

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.553

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.581 AC: 88323 AN: 152046 Hom.: 25804 Cov.: 33 AF XY: 0.578 AC XY: 42947 AN XY: 74318

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.565

Alfa AF: 0.577 Hom.: 26279

Bravo AF: 0.593

Asia WGS AF: 0.586 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.22
DANN	Benign	0.76

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: rs2071048; hg19: chr2-138721597;