Genetic Variant NM_005957.5:c.*4074_*4077delAAAA (chr1-11786602-ATTTT-A) – 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.*4074_*4077delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 142,024 control chromosomes in the GnomAD database, including 21,334 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.54 ( 21334 hom., cov: 0)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

MTHFR
NM_005957.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.308

Publications

3 publications found

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 1-11786602-ATTTT-A is Benign according to our data. Variant chr1-11786602-ATTTT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 292164.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5 link	c.4074_4077delAAAA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3	P42898-1Q8IU67Q59GJ6
C1orf167	NM_001010881.2 link	c.3568-770_3568-767delTTTT		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.4074_4077delAAAA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3		P42898-1
C1orf167	ENST00000688073.1 link	c.3568-770_3568-767delTTTT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1		A0A8I5KXP5

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

76895

AN:

141988

Hom.:

21344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.621

Gnomad MID

AF:

0.524

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

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)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.541

AC:

76883

AN:

142020

Hom.:

21334

Cov.:

AF XY:

0.546

AC XY:

37285

AN XY:

68342

show subpopulations

African (AFR)

AF:

0.386

AC:

14891

AN:

38558

American (AMR)

AF:

0.690

AC:

9884

AN:

14330

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2109

AN:

3368

East Asian (EAS)

AF:

0.758

AC:

3618

AN:

4772

South Asian (SAS)

AF:

0.453

AC:

1979

AN:

4368

European-Finnish (FIN)

AF:

0.621

AC:

4981

AN:

8024

Middle Eastern (MID)

AF:

0.522

AC:

141

AN:

270

European-Non Finnish (NFE)

AF:

0.575

AC:

37665

AN:

65480

Other (OTH)

AF:

0.554

AC:

1090

AN:

1966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

1457

2915

4372

5830

7287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.436

Hom.:

551

ClinVar

Significance: Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_005957.5:c.4074_4077delAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over