rs7349940

Positions:

• chr6-151047780-T-A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2847+10663T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,154 control chromosomes in the GnomAD database, including 1,648 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 0.10 (1648 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2847+10663T>A		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2847+10663T>A		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2850+10663T>A		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.2652+10663T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15860 AN: 152036 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152154 Hom.: 1648 Cov.: 32 AF XY: 0.107 AC XY: 7969 AN XY: 74380

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.112 Hom.: 168

Bravo AF: 0.0991

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.57

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: rs7349940; hg19: chr6-151368916;