rs803450

chr6-150942398-A-Gchr6-150942398-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.1441-2088A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1441-2088A>G		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.1444-2088A>G		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.1246-2088A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.641

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	9.7
Dann	Benign	0.80

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: rs803450; hg19: chr6-151263534;