rs17284990

Positions:

• chr15-79851855-T-C

Variant summary

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

The NM_006441.4(MTHFS):​c.380-6413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,128 control chromosomes in the GnomAD database, including 3,046 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 0.18 (3046 hom., cov: 32)
• Consequence: MTHFS NM_006441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFS	NM_006441.4	c.380-6413A>G		intron_variant		ENST00000258874.4
ST20-MTHFS	NM_001199760.2	c.308-6413A>G		intron_variant
MTHFS	NM_001199758.1	c.209-6413A>G		intron_variant
MTHFS	NR_037654.2	n.487-6413A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFS	ENST00000258874.4	c.380-6413A>G		intron_variant		1	NM_006441.4	P1
MTHFS	ENST00000559722.2	c.467-6413A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27991 AN: 152010 Hom.: 3047 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.184 AC: 27983 AN: 152128 Hom.: 3046 Cov.: 32 AF XY: 0.185 AC XY: 13766 AN XY: 74366

Gnomad4 AFR AF: 0.0937

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0600

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.184

Alfa AF: 0.215 Hom.: 4764

Bravo AF: 0.172

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.63

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: rs17284990; hg19: chr15-80144197;