Variant chr1-11805760-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005957.5(MTHFR):c.-14+128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 128,344 control chromosomes in the GnomAD database, including 159 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 0.045 ( 151 hom., cov: 31)

Exomes 𝑓: 0.043 ( 8 hom. )

Consequence

MTHFR
NM_005957.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

MTHFR 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 (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5 link	c.-14+128G>T		intron_variant		ENST00000376590.9	NP_005948.3	P42898-1Q8IU67Q59GJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9 link	c.-14+128G>T		intron_variant		1	NM_005957.5	ENSP00000365775.3		P42898-1

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

5636

AN:

124152

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.0400

Gnomad AMR

AF:

0.0463

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00276

Gnomad SAS

AF:

0.0578

Gnomad FIN

AF:

0.0417

Gnomad MID

AF:

0.0822

Gnomad NFE

AF:

0.0668

Gnomad OTH

AF:

0.0493

GnomAD4 exome

AF:

0.0434

AC:

177

AN:

4076

Hom.:

Cov.:

AF XY:

0.0459

AC XY:

AN XY:

2092

show subpopulations

Gnomad4 AFR exome

AF:

0.00575

Gnomad4 AMR exome

AF:

0.0349

Gnomad4 ASJ exome

AF:

0.0474

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0153

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0527

Gnomad4 OTH exome

AF:

0.0403

GnomAD4 genome

AF:

0.0454

AC:

5641

AN:

124268

Hom.:

151

Cov.:

AF XY:

0.0455

AC XY:

2763

AN XY:

60682

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.0462

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.00276

Gnomad4 SAS

AF:

0.0576

Gnomad4 FIN

AF:

0.0417

Gnomad4 NFE

AF:

0.0668

Gnomad4 OTH

AF:

0.0533

Alfa

AF:

0.0445

Hom.:

Bravo

AF:

0.0363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.2

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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