5-79118514-T-C

Position:

• chr5-79118514-T-C

Variant summary

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

The NM_001713.3(BHMT):​c.167-745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,132 control chromosomes in the GnomAD database, including 41,875 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 0.74 (41875 hom., cov: 33)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT	NM_001713.3	c.167-745T>C		intron_variant		ENST00000274353.10	NP_001704.2
LOC124901012	XR_007058837.1	n.79+723A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10	c.167-745T>C		intron_variant		1	NM_001713.3	ENSP00000274353.5
BHMT	ENST00000524080.1	c.166+2615T>C		intron_variant		2		ENSP00000428240.1
DMGDH	ENST00000520388.5	n.491+1827A>G		intron_variant		4
BHMT	ENST00000520703.1	n.244-745T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112259 AN: 152014 Hom.: 41827 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.739 AC: 112365 AN: 152132 Hom.: 41875 Cov.: 33 AF XY: 0.745 AC XY: 55397 AN XY: 74368

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.765

Alfa AF: 0.709 Hom.: 39173

Bravo AF: 0.751

Asia WGS AF: 0.888 AC: 3086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.50

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: rs506500; hg19: chr5-78414337;