dbSNP rs6933598: MTHFD1L:c.1394-65C>G (chr6-150938634-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015440.5(MTHFD1L):c.1394-65C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,550,708 control chromosomes in the GnomAD database, including 66,617 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 11386 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55231 hom. )

Consequence

MTHFD1L
NM_015440.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

6 publications found

Variant links:

Genes affected

MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

MTHFD1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFD1L	NM_015440.5	MANE Select	c.1394-65C>G	intron	N/A	NP_056255.2
MTHFD1L	NM_001242767.2		c.1397-65C>G	intron	N/A	NP_001229696.1	B7ZM99
MTHFD1L	NM_001242768.2		c.1199-65C>G	intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.1394-65C>G	intron	N/A	ENSP00000356290.3	Q6UB35-1
MTHFD1L	ENST00000611279.4	TSL:5	c.1397-65C>G	intron	N/A	ENSP00000478253.1	B7ZM99
MTHFD1L	ENST00000939695.1		c.1388-65C>G	intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53413

AN:

151774

Hom.:

11356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.0236

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.327

GnomAD4 exome

AF:

0.270

AC:

378194

AN:

1398816

Hom.:

55231

AF XY:

0.269

AC XY:

186526

AN XY:

693310

show subpopulations

African (AFR)

AF:

0.608

AC:

19778

AN:

32526

American (AMR)

AF:

0.381

AC:

14335

AN:

37670

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4594

AN:

25288

East Asian (EAS)

AF:

0.0168

AC:

640

AN:

38070

South Asian (SAS)

AF:

0.285

AC:

22944

AN:

80438

European-Finnish (FIN)

AF:

0.222

AC:

11319

AN:

50968

Middle Eastern (MID)

AF:

0.260

AC:

1136

AN:

4372

European-Non Finnish (NFE)

AF:

0.269

AC:

287976

AN:

1071398

Other (OTH)

AF:

0.266

AC:

15472

AN:

58086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13188

26377

39565

52754

65942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9772

19544

29316

39088

48860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.352

AC:

53508

AN:

151892

Hom.:

11386

Cov.:

AF XY:

0.349

AC XY:

25943

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.592

AC:

24505

AN:

41394

American (AMR)

AF:

0.375

AC:

5709

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

610

AN:

3472

East Asian (EAS)

AF:

0.0231

AC:

119

AN:

5154

South Asian (SAS)

AF:

0.276

AC:

1327

AN:

4816

European-Finnish (FIN)

AF:

0.219

AC:

2315

AN:

10554

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17996

AN:

67958

Other (OTH)

AF:

0.326

AC:

687

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1563

3126

4690

6253

7816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.315

Hom.:

1125

Bravo

AF:

0.371

Asia WGS

AF:

0.176

AC:

614

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.69

(source)

DANN

Benign

0.75

PhyloP100

-0.53

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over