Variant rs1256146 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005956.4(MTHFD1):c.2565+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 821,954 control chromosomes in the GnomAD database, including 13,510 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 0.17 ( 2360 hom., cov: 32)

Exomes 𝑓: 0.18 ( 11150 hom. )

Consequence

MTHFD1
NM_005956.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

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:

ZBTB25 (HGNC:13112): (zinc finger and BTB domain containing 25) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MTHFD1	NM_005956.4 linkuse as main transcript	c.2565+86G>A	intron_variant	ENST00000652337.1	NP_005947.3
ZBTB25	NM_001304508.1 linkuse as main transcript	c.174-4309C>T	intron_variant		NP_001291437.1
MTHFD1	NM_001364837.1 linkuse as main transcript	c.2565+86G>A	intron_variant		NP_001351766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1	ENST00000652337.1 linkuse as main transcript	c.2565+86G>A		intron_variant			NM_005956.4	ENSP00000498336	P1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25892

AN:

151948

Hom.:

2355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.0876

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.199

GnomAD4 exome

AF:

0.175

AC:

117498

AN:

669888

Hom.:

11150

AF XY:

0.177

AC XY:

63225

AN XY:

357182

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.0881

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0957

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.170

AC:

25908

AN:

152066

Hom.:

2360

Cov.:

AF XY:

0.166

AC XY:

12343

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0876

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.184

Hom.:

705

Bravo

AF:

0.180

Asia WGS

AF:

0.150

AC:

521

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

DANN

Benign

0.41

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

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