rs7700970

Variant names:

• chr5-79115501-C-T
• rs7700970
• NM_001713.3:c.34-266C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001713.3(BHMT):​c.34-266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,770 control chromosomes in the GnomAD database, including 8,871 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 0.33 (8871 hom., cov: 31)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 27 publications found

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]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

LOC124901012 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001713.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	NM_001713.3	MANE Select	c.34-266C>T		intron	N/A	NP_001704.2	Q93088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	ENST00000274353.10	TSL:1 MANE Select	c.34-266C>T		intron	N/A	ENSP00000274353.5	Q93088
	BHMT	ENST00000910530.1		c.34-266C>T		intron	N/A	ENSP00000580589.1
	BHMT	ENST00000910525.1		c.34-266C>T		intron	N/A	ENSP00000580584.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49642 AN: 151652 Hom.: 8842 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.328 AC: 49714 AN: 151770 Hom.: 8871 Cov.: 31 AF XY: 0.322 AC XY: 23903 AN XY: 74194

African (AFR) AF: 0.465 AC: 19184 AN: 41282

American (AMR) AF: 0.230 AC: 3514 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3470

East Asian (EAS) AF: 0.0884 AC: 458 AN: 5182

South Asian (SAS) AF: 0.278 AC: 1334 AN: 4798

European-Finnish (FIN) AF: 0.260 AC: 2744 AN: 10548

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20251 AN: 67910

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.314 Hom.: 13160

Bravo AF: 0.332

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.60
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7700970; hg19: chr5-78411324;