chr6-150989919-C-G

Variant names:

• chr6-150989919-C-G
• rs491552
• NM_015440.5:c.2125+17861C>G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2125+17861C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,064 control chromosomes in the GnomAD database, including 22,905 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 0.53 (22905 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 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.2125+17861C>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2128+17861C>G		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.1930+17861C>G		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.2125+17861C>G		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.2128+17861C>G		intron	N/A	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.2119+17861C>G		intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81124 AN: 151946 Hom.: 22864 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.534 AC: 81235 AN: 152064 Hom.: 22905 Cov.: 33 AF XY: 0.534 AC XY: 39717 AN XY: 74332

African (AFR) AF: 0.699 AC: 28979 AN: 41478

American (AMR) AF: 0.628 AC: 9607 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3348 AN: 5182

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4820

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10552

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29449 AN: 67960

Other (OTH) AF: 0.547 AC: 1157 AN: 2114

Alfa AF: 0.308 Hom.: 681

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		0.28
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: rs491552; hg19: chr6-151311055;