rs2073063

chr6-150877935-A-Gchr6-150877935-A-T

Variant summary

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

The NM_015440.5(MTHFD1L):c.417+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,291,360 control chromosomes in the GnomAD database, including 144,910 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 0.50 (19444 hom., cov: 33)
  • Exomes 𝑓: 0.47 (125466 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.417+109A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.417+109A>G		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76014 AN: 151988 Hom.: 19407 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.467 AC: 531480 AN: 1139254 Hom.: 125466 AF XY: 0.464 AC XY: 268704 AN XY: 579306

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.500 AC: 76112 AN: 152106 Hom.: 19444 Cov.: 33 AF XY: 0.498 AC XY: 37071 AN XY: 74372

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.505

Alfa AF: 0.466 Hom.: 30708

Bravo AF: 0.512

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.8
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2073063; hg19: chr6-151199071; COSMIC: COSV66208435;