chr6-151018306-C-A

Variant names:

• chr6-151018306-C-A
• rs487637
• NM_015440.5:c.2586+2613C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):​c.2586+2613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,188 control chromosomes in the GnomAD database, including 48,951 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 0.80 (48951 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.2586+2613C>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2589+2613C>A		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.2391+2613C>A		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.2586+2613C>A		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.2589+2613C>A		intron	N/A	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.2580+2613C>A		intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120886 AN: 152068 Hom.: 48902 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.795 AC: 120996 AN: 152188 Hom.: 48951 Cov.: 33 AF XY: 0.796 AC XY: 59244 AN XY: 74388

African (AFR) AF: 0.948 AC: 39381 AN: 41546

American (AMR) AF: 0.779 AC: 11915 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3470

East Asian (EAS) AF: 0.895 AC: 4638 AN: 5180

South Asian (SAS) AF: 0.704 AC: 3392 AN: 4820

European-Finnish (FIN) AF: 0.782 AC: 8270 AN: 10574

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48306 AN: 67994

Other (OTH) AF: 0.784 AC: 1655 AN: 2110

Alfa AF: 0.749 Hom.: 88281

Bravo AF: 0.803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.91
DANN	Benign	0.70
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs487637; hg19: chr6-151339442;