chr5-79087640-A-G

Position:

• chr5-79087640-A-G

Variant summary

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

The ENST00000255192.8(BHMT2):​c.1011-853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,914 control chromosomes in the GnomAD database, including 22,583 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 0.53 (22583 hom., cov: 32)
• Consequence: BHMT2 ENST00000255192.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

Genes affected

BHMT2 (HGNC:1048): (betaine--homocysteine S-methyltransferase 2) Homocysteine is a sulfur-containing amino acid that plays a crucial role in methylation reactions. Transfer of the methyl group from betaine to homocysteine creates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. The protein encoded by this gene is one of two methyl transferases that can catalyze the transfer of the methyl group from betaine to homocysteine. Anomalies in homocysteine metabolism have been implicated in disorders ranging from vascular disease to neural tube birth defects such as spina bifida. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

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 (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT2	NM_017614.5	c.1011-853A>G		intron_variant		ENST00000255192.8	NP_060084.2
BHMT2	NM_001178005.2	c.819-853A>G		intron_variant			NP_001171476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT2	ENST00000255192.8	c.1011-853A>G		intron_variant		1	NM_017614.5	ENSP00000255192	P1
BHMT2	ENST00000521567.1	c.819-853A>G		intron_variant		2		ENSP00000430278
DMGDH	ENST00000520388.5	n.606+16524T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80095 AN: 151796 Hom.: 22567 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.528 AC: 80153 AN: 151914 Hom.: 22583 Cov.: 32 AF XY: 0.530 AC XY: 39309 AN XY: 74232

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.534

Alfa AF: 0.552 Hom.: 2935

Bravo AF: 0.513

Asia WGS AF: 0.547 AC: 1900 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs597560; hg19: chr5-78383463;