Variant rs1076991 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000555252.5(MTHFD1):n.13T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,610,458 control chromosomes in the GnomAD database, including 175,153 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 0.54 ( 24417 hom., cov: 33)

Exomes 𝑓: 0.45 ( 150736 hom. )

Consequence

MTHFD1
ENST00000555252.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

MTHFD1 (HGNC:7432): (methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1) This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]

MTHFD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0874219E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1	NM_005956.4 linkuse as main transcript			upstream_gene_variant		ENST00000652337.1
MTHFD1	NM_001364837.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1	ENST00000652337.1 linkuse as main transcript			upstream_gene_variant			NM_005956.4	P1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81667

AN:

152006

Hom.:

24378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.529

GnomAD3 exomes

AF:

0.453

AC:

112290

AN:

248014

Hom.:

27091

AF XY:

0.446

AC XY:

59909

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.818

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.448

AC:

653027

AN:

1458334

Hom.:

150736

Cov.:

AF XY:

0.446

AC XY:

323420

AN XY:

724888

show subpopulations

Gnomad4 AFR exome

AF:

0.832

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.433

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.537

AC:

81763

AN:

152124

Hom.:

24417

Cov.:

AF XY:

0.527

AC XY:

39156

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.814

Gnomad4 AMR

AF:

0.468

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.414

Hom.:

2523

Bravo

AF:

0.560

TwinsUK

AF:

0.448

AC:

1663

ALSPAC

AF:

0.434

AC:

1674

ExAC

AF:

0.459

AC:

55710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.25

Dann

Benign

0.41

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.027

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P

PROVEAN

Benign

-0.040

N;.

REVEL

Benign

0.0050

Sift

Benign

0.031

D;.

Sift4G

Uncertain

0.029

D;D

Polyphen

0.0

B;.

Vest4

0.098

MutPred

0.27

Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);

ClinPred

0.030

GERP RS

-9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over