rs6923486

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015440.5(MTHFD1L):​c.2848-21394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,108 control chromosomes in the GnomAD database, including 41,954 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 0.72 ( 41954 hom., cov: 33)

Consequence

MTHFD1L
NM_015440.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTHFD1LNM_015440.5 linkuse as main transcriptc.2848-21394A>G intron_variant ENST00000367321.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTHFD1LENST00000367321.8 linkuse as main transcriptc.2848-21394A>G intron_variant 1 NM_015440.5 P4Q6UB35-1
MTHFD1LENST00000611279.4 linkuse as main transcriptc.2851-21394A>G intron_variant 5 A1
MTHFD1LENST00000618312.4 linkuse as main transcriptc.2653-21394A>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.720
AC:
109466
AN:
151990
Hom.:
41937
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.432
Gnomad AMI
AF:
0.758
Gnomad AMR
AF:
0.818
Gnomad ASJ
AF:
0.848
Gnomad EAS
AF:
0.911
Gnomad SAS
AF:
0.878
Gnomad FIN
AF:
0.816
Gnomad MID
AF:
0.829
Gnomad NFE
AF:
0.824
Gnomad OTH
AF:
0.769
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.720
AC:
109510
AN:
152108
Hom.:
41954
Cov.:
33
AF XY:
0.725
AC XY:
53931
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.432
Gnomad4 AMR
AF:
0.818
Gnomad4 ASJ
AF:
0.848
Gnomad4 EAS
AF:
0.911
Gnomad4 SAS
AF:
0.878
Gnomad4 FIN
AF:
0.816
Gnomad4 NFE
AF:
0.824
Gnomad4 OTH
AF:
0.773
Alfa
AF:
0.815
Hom.:
69421
Bravo
AF:
0.710
Asia WGS
AF:
0.869
AC:
3020
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
4.6
DANN
Benign
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6923486; hg19: chr6-151392209; API