rs17367504

Variant names:

• chr1-11802721-A-G
• rs17367504
• NM_005957.5:c.236+160T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005957.5(MTHFR):​c.236+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,172 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1508 hom., cov: 32)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• Publications: 171 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: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-11802721-A-G is Benign according to our data. Variant chr1-11802721-A-G is described in ClinVar as Benign. ClinVar VariationId is 1237104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005957.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	NM_005957.5	MANE Select	c.236+160T>C		intron	N/A	NP_005948.3
	MTHFR	NM_001330358.2		c.359+160T>C		intron	N/A	NP_001317287.1	P42898-2
	MTHFR	NM_001410750.1		c.356+160T>C		intron	N/A	NP_001397679.1	Q5SNW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	ENST00000376590.9	TSL:1 MANE Select	c.236+160T>C		intron	N/A	ENSP00000365775.3	P42898-1
	MTHFR	ENST00000423400.7	TSL:1	c.356+160T>C		intron	N/A	ENSP00000398908.3	Q5SNW7
	MTHFR	ENST00000376592.6	TSL:1	c.236+160T>C		intron	N/A	ENSP00000365777.1	P42898-1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20735 AN: 152054 Hom.: 1512 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20735 AN: 152172 Hom.: 1508 Cov.: 32 AF XY: 0.138 AC XY: 10256 AN XY: 74382

African (AFR) AF: 0.111 AC: 4619 AN: 41532

American (AMR) AF: 0.106 AC: 1618 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.125 AC: 646 AN: 5172

South Asian (SAS) AF: 0.198 AC: 956 AN: 4830

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10558 AN: 67984

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.146 Hom.: 7725

Bravo AF: 0.130

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.069
DANN	Benign	0.44
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs17367504; hg19: chr1-11862778;