NM_015440.5:c.2848-19489G>A

Variant names:

• chr6-151072978-G-A
• rs12524884
• NM_015440.5:c.2848-19489G>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.2848-19489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 148,386 control chromosomes in the GnomAD database, including 1,684 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 0.14 (1684 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 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.2848-19489G>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2851-19489G>A		intron	N/A	NP_001229696.1
	MTHFD1L	NM_001242768.2		c.2653-19489G>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.2848-19489G>A		intron	N/A	ENSP00000356290.3
	MTHFD1L	ENST00000611279.4	TSL:5	c.2851-19489G>A		intron	N/A	ENSP00000478253.1
	MTHFD1L	ENST00000618312.4	TSL:5	c.2653-19489G>A		intron	N/A	ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 20585 AN: 148280 Hom.: 1684 Cov.: 31

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.139 AC: 20578 AN: 148386 Hom.: 1684 Cov.: 31 AF XY: 0.141 AC XY: 10175 AN XY: 72348

African (AFR) AF: 0.0528 AC: 2102 AN: 39800

American (AMR) AF: 0.136 AC: 2004 AN: 14728

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 517 AN: 3450

East Asian (EAS) AF: 0.0817 AC: 419 AN: 5128

South Asian (SAS) AF: 0.165 AC: 719 AN: 4346

European-Finnish (FIN) AF: 0.226 AC: 2342 AN: 10344

Middle Eastern (MID) AF: 0.115 AC: 33 AN: 286

European-Non Finnish (NFE) AF: 0.179 AC: 12079 AN: 67350

Other (OTH) AF: 0.135 AC: 276 AN: 2044

Alfa AF: 0.148 Hom.: 2224

Bravo AF: 0.121

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		0.031
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: rs12524884; hg19: chr6-151394114; COSMIC: COSV66227103;