2-137993448-A-G

Position:

• chr2-137993448-A-G

Variant summary

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

The NM_006895.3(HNMT):​c.191-7470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,784 control chromosomes in the GnomAD database, including 13,804 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 0.42 (13804 hom., cov: 31)
• Consequence: HNMT NM_006895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

HNMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNMT	NM_006895.3	c.191-7470A>G		intron_variant		ENST00000280097.5	NP_008826.1
HNMT	XM_017003948.2	c.89-7470A>G		intron_variant			XP_016859437.1
HNMT	XM_011511064.3	c.-188-7470A>G		intron_variant			XP_011509366.1
HNMT	XM_017003949.3	c.191-7470A>G		intron_variant			XP_016859438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNMT	ENST00000280097.5	c.191-7470A>G		intron_variant		1	NM_006895.3	ENSP00000280097.3
HNMT	ENST00000410115.5	c.191-7470A>G		intron_variant		5		ENSP00000386940.1
HNMT	ENST00000467390.5	n.203-7470A>G		intron_variant		2
HNMT	ENST00000485653.1	n.123-7470A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64020 AN: 151666 Hom.: 13790 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.422 AC: 64090 AN: 151784 Hom.: 13804 Cov.: 31 AF XY: 0.427 AC XY: 31701 AN XY: 74202

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.450

Alfa AF: 0.283 Hom.: 696

Bravo AF: 0.421

Asia WGS AF: 0.462 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3100722; hg19: chr2-138751018;