rs9371491

chr6-151052519-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.2847+15402A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,134 control chromosomes in the GnomAD database, including 1,986 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 0.13 (1986 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2847+15402A>T		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2847+15402A>T		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2850+15402A>T		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.2652+15402A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19744 AN: 152016 Hom.: 1984 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.130 AC: 19754 AN: 152134 Hom.: 1986 Cov.: 32 AF XY: 0.131 AC XY: 9749 AN XY: 74354

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.129

Alfa AF: 0.137 Hom.: 213

Bravo AF: 0.134

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.8
Dann	Benign	0.85

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: rs9371491; hg19: chr6-151373655;