rs1113983

chr15-79874255-C-A

Variant summary

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

The NM_006441.4(MTHFS):c.379+14838G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,532 control chromosomes in the GnomAD database, including 14,086 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 0.42 (14086 hom., cov: 32)
• Consequence: MTHFS NM_006441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFS	NM_006441.4	c.379+14838G>T		intron_variant		ENST00000258874.4
ST20-MTHFS	NM_001199760.2	c.307+14838G>T		intron_variant
MTHFS	NM_001199758.1	c.208+14838G>T		intron_variant
MTHFS	NR_037654.2	n.486+14838G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFS	ENST00000258874.4	c.379+14838G>T		intron_variant		1	NM_006441.4	P1
MTHFS	ENST00000559722.2	c.466+14838G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64205 AN: 151414 Hom.: 14055 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.424 AC: 64281 AN: 151532 Hom.: 14086 Cov.: 32 AF XY: 0.428 AC XY: 31653 AN XY: 74028

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.401

Alfa AF: 0.415 Hom.: 2255

Bravo AF: 0.427

Asia WGS AF: 0.488 AC: 1698 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	0.53
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: rs1113983; hg19: chr15-80166597;