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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFS	NM_006441.4	c.379+7047G>T		intron_variant	Intron 2 of 2	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2	c.307+7047G>T		intron_variant	Intron 3 of 3		NP_001186689.1
MTHFS	NM_001199758.1	c.208+7047G>T		intron_variant	Intron 2 of 2		NP_001186687.1
MTHFS	NR_037654.2	n.486+7047G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000258874.4	c.379+7047G>T		intron_variant	Intron 2 of 2	1	NM_006441.4	ENSP00000258874.4
ST20-MTHFS	ENST00000479961.1	c.307+7047G>T		intron_variant	Intron 3 of 3	3		ENSP00000455643.1

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

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.466

Alfa AF: 0.507 Hom.: 27380

Bravo AF: 0.441

Asia WGS AF: 0.450 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.67

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: rs2562744; hg19: chr15-80174388;