rs1738567

Positions:

• chr6-150968040-C-A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2013+3003C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,220 control chromosomes in the GnomAD database, including 16,598 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 0.46 (16598 hom., cov: 29)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2013+3003C>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.2013+3003C>A		intron_variant		1	NM_015440.5	ENSP00000356290	P4
MTHFD1L	ENST00000611279.4	c.2016+3003C>A		intron_variant		5		ENSP00000478253	A1
MTHFD1L	ENST00000618312.4	c.1818+3003C>A		intron_variant		5		ENSP00000479539

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68950 AN: 151100 Hom.: 16610 Cov.: 29

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.431

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.456 AC: 68956 AN: 151220 Hom.: 16598 Cov.: 29 AF XY: 0.457 AC XY: 33764 AN XY: 73864

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.442

Alfa AF: 0.492 Hom.: 2375

Bravo AF: 0.435

Asia WGS AF: 0.422 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.82

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: rs1738567; hg19: chr6-151289176; COSMIC: COSV66227246; COSMIC: COSV66227246;