rs6923486

Variant names:

• chr6-151071073-A-G
• rs6923486
• NM_015440.5:c.2848-21394A>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.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
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.2848-21394A>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2851-21394A>G		intron	N/A	NP_001229696.1
	MTHFD1L	NM_001242768.2		c.2653-21394A>G		intron	N/A	NP_001229697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.2848-21394A>G		intron	N/A	ENSP00000356290.3
	MTHFD1L	ENST00000611279.4	TSL:5	c.2851-21394A>G		intron	N/A	ENSP00000478253.1
	MTHFD1L	ENST00000618312.4	TSL:5	c.2653-21394A>G		intron	N/A	ENSP00000479539.1

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

African (AFR) AF: 0.432 AC: 17904 AN: 41482

American (AMR) AF: 0.818 AC: 12497 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2945 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4713 AN: 5172

South Asian (SAS) AF: 0.878 AC: 4238 AN: 4828

European-Finnish (FIN) AF: 0.816 AC: 8626 AN: 10576

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56020 AN: 67990

Other (OTH) AF: 0.773 AC: 1632 AN: 2112

Alfa AF: 0.802 Hom.: 85685

Bravo AF: 0.710

Asia WGS AF: 0.869 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		-0.048
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: rs6923486; hg19: chr6-151392209;