rs803450

Variant names:

• chr6-150942398-A-G
• rs803450
• NM_015440.5:c.1441-2088A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-150942398-A-G
• chr6-150942398-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):​c.1441-2088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,134 control chromosomes in the GnomAD database, including 31,751 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 0.64 (31751 hom., cov: 34)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.78 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.1441-2088A>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.1444-2088A>G		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.1246-2088A>G		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.1441-2088A>G		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.1444-2088A>G		intron	N/A	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.1435-2088A>G		intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97015 AN: 152016 Hom.: 31703 Cov.: 34

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.638 AC: 97121 AN: 152134 Hom.: 31751 Cov.: 34 AF XY: 0.637 AC XY: 47348 AN XY: 74348

African (AFR) AF: 0.787 AC: 32664 AN: 41512

American (AMR) AF: 0.644 AC: 9843 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1980 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2943 AN: 5182

South Asian (SAS) AF: 0.686 AC: 3307 AN: 4822

European-Finnish (FIN) AF: 0.515 AC: 5437 AN: 10550

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38977 AN: 67996

Other (OTH) AF: 0.641 AC: 1353 AN: 2112

Alfa AF: 0.611 Hom.: 3620

Bravo AF: 0.654

Asia WGS AF: 0.633 AC: 2201 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	9.7
DANN	Benign	0.80
PhyloP100		0.15
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: rs803450; hg19: chr6-151263534;