2-137964027-C-T

Variant names:

• chr2-137964027-C-T
• rs2071048
• ENST00000410115:c.-141C>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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNMT	ENST00000410115	c.-141C>T		5_prime_UTR_variant	Exon 1 of 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;