6-150876016-C-G

Variant names:

• chr6-150876016-C-G
• rs2073067
• NM_015440.5:c.228-74C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.228-74C>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.228-74C>G		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.30-74C>G		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.228-74C>G		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000367307.8	TSL:1	c.228-74C>G		intron	N/A	ENSP00000356276.4	Q6UB35-2
	MTHFD1L	ENST00000611279.4	TSL:5	c.228-74C>G		intron	N/A	ENSP00000478253.1	B7ZM99

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

GnomAD2 exomes AF: 0.323 AC: 58451 AN: 181142 AF XY: 0.330

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 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

African (AFR) AF: 0.339 AC: 8353 AN: 24636

American (AMR) AF: 0.208 AC: 7301 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 8118 AN: 22938

East Asian (EAS) AF: 0.237 AC: 8687 AN: 36702

South Asian (SAS) AF: 0.329 AC: 23406 AN: 71174

European-Finnish (FIN) AF: 0.369 AC: 18802 AN: 50904

Middle Eastern (MID) AF: 0.373 AC: 1824 AN: 4892

European-Non Finnish (NFE) AF: 0.366 AC: 277259 AN: 756916

Other (OTH) AF: 0.360 AC: 16670 AN: 46262

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

African (AFR) AF: 0.335 AC: 13910 AN: 41484

American (AMR) AF: 0.276 AC: 4217 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5174

South Asian (SAS) AF: 0.341 AC: 1646 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3899 AN: 10556

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24975 AN: 67960

Other (OTH) AF: 0.367 AC: 776 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.35
PhyloP100		-0.12
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: rs2073067; hg19: chr6-151197152; COSMIC: COSV66208681;