rs1246590

chr4-74232992-C-T

Variant summary

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

The NM_001144978.3(MTHFD2L):c.805+7598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,608 control chromosomes in the GnomAD database, including 6,214 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 0.28 (6214 hom., cov: 32)
• Consequence: MTHFD2L NM_001144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

Genes affected

MTHFD2L (HGNC:31865): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like) Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Predicted to be located in mitochondrial matrix. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD2L	NM_001144978.3	c.805+7598C>T		intron_variant		ENST00000325278.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD2L	ENST00000325278.7	c.805+7598C>T		intron_variant		5	NM_001144978.3	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41741 AN: 151490 Hom.: 6202 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.276 AC: 41799 AN: 151608 Hom.: 6214 Cov.: 32 AF XY: 0.276 AC XY: 20449 AN XY: 74076

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.264

Alfa AF: 0.243 Hom.: 951

Bravo AF: 0.285

Asia WGS AF: 0.237 AC: 827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.3
Dann	Benign	0.68

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: rs1246590; hg19: chr4-75098709;