rs492842

Positions:

• chr5-79114164-C-T

Variant summary

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

The NM_001713.3(BHMT):​c.34-1603C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 149,932 control chromosomes in the GnomAD database, including 26,373 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 0.59 (26373 hom., cov: 29)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT	NM_001713.3	c.34-1603C>T		intron_variant		ENST00000274353.10	NP_001704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10	c.34-1603C>T		intron_variant		1	NM_001713.3	ENSP00000274353	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 88180 AN: 149882 Hom.: 26353 Cov.: 29

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.588 AC: 88220 AN: 149932 Hom.: 26373 Cov.: 29 AF XY: 0.590 AC XY: 43178 AN XY: 73136

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.584

Alfa AF: 0.607 Hom.: 37461

Bravo AF: 0.580

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.63

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: rs492842; hg19: chr5-78409987; COSMIC: COSV57153914;