rs2073067

Positions:

• chr6-150876016-C-G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.228-74C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,201,496 control chromosomes in the GnomAD database, including 76,078 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 0.34 (9162 hom., cov: 32)
  • Exomes 𝑓: 0.35 (66916 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.228-74C>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.228-74C>G		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52258 AN: 151920 Hom.: 9155 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.323 AC: 58451 AN: 181142 Hom.: 10000 AF XY: 0.330 AC XY: 32041 AN XY: 97086

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.353 AC: 370420 AN: 1049458 Hom.: 66916 Cov.: 13 AF XY: 0.353 AC XY: 188749 AN XY: 535216

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.344 AC: 52300 AN: 152038 Hom.: 9162 Cov.: 32 AF XY: 0.341 AC XY: 25357 AN XY: 74300

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.367

Alfa AF: 0.351 Hom.: 1749

Bravo AF: 0.334

Asia WGS AF: 0.315 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.35

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: rs2073067; hg19: chr6-151197152; COSMIC: COSV66208681;