dbSNP rs7700970: BHMT:c.34-266C>T (chr5-79115501-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

Publications

27 publications found

Variant links:

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]

BHMT links:

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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

DMGDH links:

LOC124901012 (HGNC:):

LOC124901012 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHMT	NM_001713.3 link	c.34-266C>T		intron_variant	Intron 1 of 7	ENST00000274353.10	NP_001704.2	Q93088V9HWA4
LOC124901012	XR_007058837.1 link	n.80-203G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10 link	c.34-266C>T		intron_variant	Intron 1 of 7	1	NM_001713.3	ENSP00000274353.5		Q93088

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49642

AN:

151652

Hom.:

8842

Cov.:

show subpopulations

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.:

AF XY:

0.322

AC XY:

23903

AN XY:

74194

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1626

3252

4878

6504

8130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.3

(source)

DANN

Benign

0.60

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over