rs2073066

Positions:

• chr6-150876595-A-G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.312+421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,216 control chromosomes in the GnomAD database, including 2,281 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 0.17 (2281 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.18

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.312+421A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.312+421A>G		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25365 AN: 152098 Hom.: 2284 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.167 AC: 25364 AN: 152216 Hom.: 2281 Cov.: 32 AF XY: 0.170 AC XY: 12620 AN XY: 74416

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.165

Alfa AF: 0.183 Hom.: 5360

Bravo AF: 0.154

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0020
DANN	Benign	0.47

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: rs2073066; hg19: chr6-151197731;