rs55686944

Positions:

• chr1-11791128-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005957.5(MTHFR):​c.1752+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,604,016 control chromosomes in the GnomAD database, including 2,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (166 hom., cov: 31)
  • Exomes 𝑓: 0.055 (2436 hom.)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.692

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-11791128-C-T is Benign according to our data. Variant chr1-11791128-C-T is described in ClinVar as [Benign]. Clinvar id is 1224664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.1752+79G>A		intron_variant		ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.1752+79G>A		intron_variant		1	NM_005957.5	ENSP00000365775.3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5617 AN: 152154 Hom.: 166 Cov.: 31

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0545

GnomAD4 exome AF: 0.0553 AC: 80234 AN: 1451744 Hom.: 2436 AF XY: 0.0566 AC XY: 40861 AN XY: 721868

Gnomad4 AFR exome AF: 0.00908

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0595

Gnomad4 OTH exome AF: 0.0509

GnomAD4 genome AF: 0.0369 AC: 5613 AN: 152272 Hom.: 166 Cov.: 31 AF XY: 0.0362 AC XY: 2695 AN XY: 74460

Gnomad4 AFR AF: 0.00919

Gnomad4 AMR AF: 0.0349

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0735

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0511 Hom.: 62

Bravo AF: 0.0365

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs55686944; hg19: chr1-11851185;