rs11754661

Positions:

• chr6-150885942-G-A
• chr6-150885942-G-T

Variant summary

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

The NM_015440.5(MTHFD1L):​c.643+208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 152,202 control chromosomes in the GnomAD database, including 213 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 0.049 (213 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

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 (NFE) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.643+208G>A		intron_variant		ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.643+208G>A		intron_variant		1	NM_015440.5	ENSP00000356290	P4

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7418 AN: 152084 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0487 AC: 7419 AN: 152202 Hom.: 213 Cov.: 32 AF XY: 0.0474 AC XY: 3531 AN XY: 74426

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0616 Hom.: 447

Bravo AF: 0.0457

Asia WGS AF: 0.0320 AC: 113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.71

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: rs11754661; hg19: chr6-151207078;