rs2073063

Variant names:

• chr6-150877935-A-G
• rs2073063
• NM_015440.5:c.417+109A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-150877935-A-G
• chr6-150877935-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.84).
• 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 rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.417+109A>G		intron_variant	Intron 4 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.417+109A>G		intron_variant	Intron 4 of 27	1	NM_015440.5	ENSP00000356290.3

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

African (AFR) AF: 0.586 AC: 15522 AN: 26480

American (AMR) AF: 0.536 AC: 21218 AN: 39570

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 11273 AN: 23470

East Asian (EAS) AF: 0.436 AC: 16525 AN: 37918

South Asian (SAS) AF: 0.416 AC: 31936 AN: 76702

European-Finnish (FIN) AF: 0.452 AC: 23405 AN: 51744

Middle Eastern (MID) AF: 0.433 AC: 1897 AN: 4384

European-Non Finnish (NFE) AF: 0.465 AC: 386048 AN: 829510

Other (OTH) AF: 0.478 AC: 23656 AN: 49476

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

African (AFR) AF: 0.584 AC: 24229 AN: 41492

American (AMR) AF: 0.511 AC: 7813 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2235 AN: 5182

South Asian (SAS) AF: 0.425 AC: 2049 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4768 AN: 10562

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31491 AN: 67972

Other (OTH) AF: 0.505 AC: 1067 AN: 2114

Alfa AF: 0.476 Hom.: 51701

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
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2073063; hg19: chr6-151199071; COSMIC: COSV66208435;