rs622506

Positions:

• chr15-79846853-A-C

Variant summary

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

The NM_006441.4(MTHFS):​c.380-1411T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,068 control chromosomes in the GnomAD database, including 9,574 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 0.34 (9574 hom., cov: 33)
• Consequence: MTHFS NM_006441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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 = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFS	NM_006441.4	c.380-1411T>G		intron_variant		ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2	c.308-1411T>G		intron_variant			NP_001186689.1
MTHFS	NM_001199758.1	c.209-1411T>G		intron_variant			NP_001186687.1
MTHFS	NR_037654.2	n.487-1411T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000258874.4	c.380-1411T>G		intron_variant		1	NM_006441.4	ENSP00000258874	P1
MTHFS	ENST00000559722.2	c.467-1411T>G		intron_variant		2		ENSP00000489076

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51422 AN: 151950 Hom.: 9572 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.338 AC: 51438 AN: 152068 Hom.: 9574 Cov.: 33 AF XY: 0.342 AC XY: 25448 AN XY: 74318

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.332

Alfa AF: 0.329 Hom.: 1259

Bravo AF: 0.331

Asia WGS AF: 0.445 AC: 1545 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	1.4
DANN	Benign	0.44

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: rs622506; hg19: chr15-80139195;