rs12524884

Positions:

• chr6-151072978-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2848-19489G>A		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2848-19489G>A		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2851-19489G>A		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.2653-19489G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.135

Alfa AF: 0.159 Hom.: 1662

Bravo AF: 0.121

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs12524884; hg19: chr6-151394114; COSMIC: COSV66227103;