rs2586179

Positions:

• chr15-79895664-G-T

Variant summary

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

The NM_006441.4(MTHFS):​c.117+1208C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,034 control chromosomes in the GnomAD database, including 16,136 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 0.45 (16136 hom., cov: 33)
• Consequence: MTHFS NM_006441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

MTHFS (HGNC:7437): (methenyltetrahydrofolate synthetase) The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ST20-MTHFS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFS	NM_006441.4	c.117+1208C>A		intron_variant		ENST00000258874.4
ST20-MTHFS	NM_001199760.2	c.46-6310C>A		intron_variant
MTHFS	NM_001199758.1	c.-55+1497C>A		intron_variant
MTHFS	NR_037654.2	n.224+1127C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFS	ENST00000258874.4	c.117+1208C>A		intron_variant		1	NM_006441.4	P1
	ENST00000655674.1	n.1032C>A		non_coding_transcript_exon_variant	1/1
MTHFS	ENST00000559722.2	c.204+1497C>A		intron_variant		2
MTHFS	ENST00000560919.5	c.*63+1127C>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68342 AN: 151918 Hom.: 16121 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.450 AC: 68379 AN: 152034 Hom.: 16136 Cov.: 33 AF XY: 0.448 AC XY: 33314 AN XY: 74294

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.467

Alfa AF: 0.497 Hom.: 3906

Bravo AF: 0.442

Asia WGS AF: 0.455 AC: 1581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.41

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: rs2586179; hg19: chr15-80188006;