rs694290

chr5-79125957-G-Achr5-79125957-G-Cchr5-79125957-G-T

Variant summary

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

The NM_001713.3(BHMT):c.626-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,371,326 control chromosomes in the GnomAD database, including 328,716 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 0.67 (34364 hom., cov: 30)
  • Exomes 𝑓: 0.69 (294352 hom.)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

DMGDH (HGNC:24475): (dimethylglycine dehydrogenase) This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT	NM_001713.3	c.626-89G>A		intron_variant		ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10	c.626-89G>A		intron_variant		1	NM_001713.3	P1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101254 AN: 151746 Hom.: 34339 Cov.: 30

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.693 AC: 844553 AN: 1219462 Hom.: 294352 AF XY: 0.696 AC XY: 419229 AN XY: 602098

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.667 AC: 101330 AN: 151864 Hom.: 34364 Cov.: 30 AF XY: 0.674 AC XY: 50038 AN XY: 74214

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.699

Alfa AF: 0.680 Hom.: 39906

Bravo AF: 0.671

Asia WGS AF: 0.816 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.83
Dann	Benign	0.42

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: rs694290; hg19: chr5-78421780;