rs1982494

Positions:

• chr2-137971543-G-A
• chr2-137971543-G-T

Variant summary

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

The NM_006895.3(HNMT):​c.190+1326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,912 control chromosomes in the GnomAD database, including 22,256 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 0.53 (22256 hom., cov: 31)
• Consequence: HNMT NM_006895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNMT	NM_006895.3	c.190+1326G>A		intron_variant		ENST00000280097.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5	c.190+1326G>A		intron_variant		1	NM_006895.3	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80767 AN: 151794 Hom.: 22250 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.532 AC: 80803 AN: 151912 Hom.: 22256 Cov.: 31 AF XY: 0.531 AC XY: 39375 AN XY: 74220

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.527

Alfa AF: 0.576 Hom.: 23368

Bravo AF: 0.537

Asia WGS AF: 0.579 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.8
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: rs1982494; hg19: chr2-138729113;