rs11757561

Positions:

• chr6-150872315-A-G
• chr6-150872315-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.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

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=-0.98).
• 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/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.228-3775A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.228-3775A>G		intron_variant		1	NM_015440.5	P4

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

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.238

Alfa AF: 0.208 Hom.: 4723

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

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: rs11757561; hg19: chr6-151193451;