NM_015440.5:c.228-3775A>G

Variant names:

• chr6-150872315-A-G
• rs11757561
• NM_015440.5:c.228-3775A>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.228-3775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,016 control chromosomes in the GnomAD database, including 6,801 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 0.28 (6801 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.228-3775A>G		intron_variant	Intron 1 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.228-3775A>G		intron_variant	Intron 1 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42769 AN: 151898 Hom.: 6789 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.282 AC: 42822 AN: 152016 Hom.: 6801 Cov.: 32 AF XY: 0.286 AC XY: 21277 AN XY: 74316

African (AFR) AF: 0.395 AC: 16352 AN: 41444

American (AMR) AF: 0.300 AC: 4581 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 650 AN: 3466

East Asian (EAS) AF: 0.429 AC: 2218 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4812

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10548

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13685 AN: 67996

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.217 Hom.: 6542

Bravo AF: 0.293

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-1.8
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: rs11757561; hg19: chr6-151193451;