NM_015440.5:c.643+208G>A

Variant names:

• chr6-150885942-G-A
• rs11754661
• NM_015440.5:c.643+208G>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.643+208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 152,202 control chromosomes in the GnomAD database, including 213 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 0.049 (213 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 40 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 (NFE) allele frequency at 95% confidence interval = 0.0697 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.643+208G>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.643+208G>A		intron	N/A	NP_001229696.1
	MTHFD1L	NM_001242768.2		c.445+208G>A		intron	N/A	NP_001229697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.643+208G>A		intron	N/A	ENSP00000356290.3
	MTHFD1L	ENST00000367307.8	TSL:1	c.643+208G>A		intron	N/A	ENSP00000356276.4
	MTHFD1L	ENST00000611279.4	TSL:5	c.643+208G>A		intron	N/A	ENSP00000478253.1

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7418 AN: 152084 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0487 AC: 7419 AN: 152202 Hom.: 213 Cov.: 32 AF XY: 0.0474 AC XY: 3531 AN XY: 74426

African (AFR) AF: 0.0142 AC: 590 AN: 41538

American (AMR) AF: 0.0480 AC: 734 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5178

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4824

European-Finnish (FIN) AF: 0.0448 AC: 475 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0714 AC: 4853 AN: 67996

Other (OTH) AF: 0.0531 AC: 112 AN: 2108

Alfa AF: 0.0599 Hom.: 1013

Bravo AF: 0.0457

Asia WGS AF: 0.0320 AC: 113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.71
PhyloP100		-0.34
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: rs11754661; hg19: chr6-151207078;