rs6923486

chr6-151071073-A-G

Variant summary

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

The NM_015440.5(MTHFD1L):c.2848-21394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,108 control chromosomes in the GnomAD database, including 41,954 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 0.72 (41954 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2848-21394A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2848-21394A>G		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2851-21394A>G		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.2653-21394A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109466 AN: 151990 Hom.: 41937 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.720 AC: 109510 AN: 152108 Hom.: 41954 Cov.: 33 AF XY: 0.725 AC XY: 53931 AN XY: 74348

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.773

Alfa AF: 0.815 Hom.: 69421

Bravo AF: 0.710

Asia WGS AF: 0.869 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.6
Dann	Benign	0.55

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: rs6923486; hg19: chr6-151392209;