rs2562744

Variant names:

• chr15-79882046-C-A
• rs2562744
• NM_006441.4:c.379+7047G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-79882046-C-A
• chr15-79882046-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006441.4(MTHFS):​c.379+7047G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,114 control chromosomes in the GnomAD database, including 16,095 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 (16095 hom., cov: 33)
• Consequence: MTHFS NM_006441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 5 publications found

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:44655): (ST20-MTHFS readthrough) This locus represents naturally occurring read-through transcription between the neighboring suppressor of tumorigenicity 20 and 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) genes on chromosome 15. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006441.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFS	NM_006441.4	MANE Select	c.379+7047G>T		intron	N/A	NP_006432.1
	ST20-MTHFS	NM_001199760.2		c.307+7047G>T		intron	N/A	NP_001186689.1
	MTHFS	NM_001199758.1		c.208+7047G>T		intron	N/A	NP_001186687.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFS	ENST00000258874.4	TSL:1 MANE Select	c.379+7047G>T		intron	N/A	ENSP00000258874.4
	ST20-MTHFS	ENST00000479961.1	TSL:3	c.307+7047G>T		intron	N/A	ENSP00000455643.1
	MTHFS	ENST00000559722.2	TSL:2	c.466+7047G>T		intron	N/A	ENSP00000489076.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68217 AN: 151996 Hom.: 16079 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.449 AC: 68255 AN: 152114 Hom.: 16095 Cov.: 33 AF XY: 0.447 AC XY: 33257 AN XY: 74352

African (AFR) AF: 0.305 AC: 12665 AN: 41498

American (AMR) AF: 0.477 AC: 7298 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2395 AN: 5166

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4824

European-Finnish (FIN) AF: 0.470 AC: 4964 AN: 10570

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.522 AC: 35455 AN: 67974

Other (OTH) AF: 0.466 AC: 984 AN: 2112

Alfa AF: 0.502 Hom.: 61326

Bravo AF: 0.441

Asia WGS AF: 0.450 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.67
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2562744; hg19: chr15-80174388;