rs1738574

Positions:

• chr6-150965834-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):​c.2013+797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,982 control chromosomes in the GnomAD database, including 17,915 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 0.47 (17915 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2013+797A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2013+797A>G		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2016+797A>G		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.1818+797A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71837 AN: 151864 Hom.: 17928 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.473 AC: 71846 AN: 151982 Hom.: 17915 Cov.: 32 AF XY: 0.473 AC XY: 35168 AN XY: 74294

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.461

Alfa AF: 0.492 Hom.: 2764

Bravo AF: 0.451

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.88

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: rs1738574; hg19: chr6-151286970; COSMIC: COSV66227232;