rs7765521

Positions:

• chr6-150883407-A-G
• chr6-150883407-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.542+521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,974 control chromosomes in the GnomAD database, including 23,369 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 0.55 (23369 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.542+521A>G		intron_variant		ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.542+521A>G		intron_variant		1	NM_015440.5	ENSP00000356290	P4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83599 AN: 151856 Hom.: 23332 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.551 AC: 83696 AN: 151974 Hom.: 23369 Cov.: 31 AF XY: 0.550 AC XY: 40849 AN XY: 74268

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.545

Alfa AF: 0.535 Hom.: 4815

Bravo AF: 0.559

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.46

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: rs7765521; hg19: chr6-151204543;