rs55686944

Variant names:

• chr1-11791128-C-T
• rs55686944
• NM_005957.5:c.1752+79G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330358.2(MTHFR):​c.1875+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_001330358.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.692
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• homocystinuria due to methylene tetrahydrofolate reductase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330358.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	NM_005957.5	MANE Select	c.1752+79G>A		intron	N/A	NP_005948.3
	MTHFR	NM_001330358.2		c.1875+79G>A		intron	N/A	NP_001317287.1
	MTHFR	NM_001410750.1		c.1872+79G>A		intron	N/A	NP_001397679.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	ENST00000376590.9	TSL:1 MANE Select	c.1752+79G>A		intron	N/A	ENSP00000365775.3
	MTHFR	ENST00000423400.7	TSL:1	c.1872+79G>A		intron	N/A	ENSP00000398908.3
	MTHFR	ENST00000376592.6	TSL:1	c.1752+79G>A		intron	N/A	ENSP00000365777.1

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

African (AFR) AF: 0.00908 AC: 302 AN: 33246

American (AMR) AF: 0.0252 AC: 1124 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 1196 AN: 25860

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39602

South Asian (SAS) AF: 0.0843 AC: 7218 AN: 85662

European-Finnish (FIN) AF: 0.0230 AC: 1222 AN: 53236

Middle Eastern (MID) AF: 0.0747 AC: 406 AN: 5438

European-Non Finnish (NFE) AF: 0.0595 AC: 65703 AN: 1104078

Other (OTH) AF: 0.0509 AC: 3057 AN: 60044

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

African (AFR) AF: 0.00919 AC: 382 AN: 41558

American (AMR) AF: 0.0349 AC: 534 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0735 AC: 354 AN: 4818

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0567 AC: 3856 AN: 68008

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0515 Hom.: 380

Bravo AF: 0.0365

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.78
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55686944; hg19: chr1-11851185;