rs626105

Positions:

• chr5-79074078-A-G
• chr5-79074078-A-T

Variant summary

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

The NM_017614.5(BHMT2):​c.34-3402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,092 control chromosomes in the GnomAD database, including 40,531 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 0.72 (40531 hom., cov: 31)
• Consequence: BHMT2 NM_017614.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

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]

BHMT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT2	NM_017614.5	c.34-3402A>G		intron_variant		ENST00000255192.8	NP_060084.2
BHMT2	NM_001178005.2	c.34-3402A>G		intron_variant			NP_001171476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT2	ENST00000255192.8	c.34-3402A>G		intron_variant		1	NM_017614.5	ENSP00000255192.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110013 AN: 151974 Hom.: 40503 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.724 AC: 110085 AN: 152092 Hom.: 40531 Cov.: 31 AF XY: 0.724 AC XY: 53856 AN XY: 74346

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.726

Alfa AF: 0.768 Hom.: 20624

Bravo AF: 0.712

Asia WGS AF: 0.730 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.82

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: rs626105; hg19: chr5-78369901;