Genetic Variant MTHFR:c.*4644dupA (chr1-11786035-G-GT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005957.5(MTHFR):c.*4644dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.98 ( 72511 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

MTHFR
NM_005957.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.535

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:

C1orf167 (HGNC:25262): (chromosome 1 open reading frame 167) Implicated in coronary artery disease. [provided by Alliance of Genome Resources, Apr 2022]

C1orf167 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-11786035-G-GT is Benign according to our data. Variant chr1-11786035-G-GT is described in ClinVar as [Benign]. Clinvar id is 292153.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5 link	c.*4644dupA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3	P42898-1Q8IU67Q59GJ6
C1orf167	NM_001010881.2 link	c.3567+757dupT		intron_variant	Intron 16 of 20	ENST00000688073.1	NP_001010881.1	Q5SNV9A2VCK6A0A8I5KXP5Q8NDG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9 link	c.*4644dupA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3		P42898-1
C1orf167	ENST00000688073.1 link	c.3567+757dupT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1		A0A8I5KXP5

Frequencies

GnomAD3 genomes

AF:

0.984

AC:

147309

AN:

149702

Hom.:

72488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.962

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.976

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.986

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.984

AC:

147373

AN:

149790

Hom.:

72511

Cov.:

AF XY:

0.983

AC XY:

71732

AN XY:

72966

show subpopulations

African (AFR)

AF:

0.961

AC:

39346

AN:

40922

American (AMR)

AF:

0.994

AC:

15011

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3433

AN:

3440

East Asian (EAS)

AF:

0.997

AC:

5128

AN:

5144

South Asian (SAS)

AF:

0.999

AC:

4722

AN:

4726

European-Finnish (FIN)

AF:

0.976

AC:

9568

AN:

9802

Middle Eastern (MID)

AF:

0.993

AC:

288

AN:

290

European-Non Finnish (NFE)

AF:

0.993

AC:

66939

AN:

67402

Other (OTH)

AF:

0.986

AC:

2034

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

182

274

365

456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.993

Hom.:

2192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neural tube defects, folate-sensitive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

1-11786035-G-GT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over