chr4-74232992-C-T

Variant names:

• chr4-74232992-C-T
• rs1246590
• NM_001144978.3:c.805+7598C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	NM_001144978.3	MANE Select	c.805+7598C>T		intron	N/A	NP_001138450.1	Q9H903-4
	MTHFD2L	NM_001004346.4		c.631+7598C>T		intron	N/A	NP_001004346.2	Q9H903-1
	MTHFD2L	NM_001351310.2		c.631+7598C>T		intron	N/A	NP_001338239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	ENST00000325278.7	TSL:5 MANE Select	c.805+7598C>T		intron	N/A	ENSP00000321984.7	Q9H903-4
	MTHFD2L	ENST00000433372.5	TSL:1	n.776+7598C>T		intron	N/A
	MTHFD2L	ENST00000461856.5	TSL:1	n.173+7598C>T		intron	N/A

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

African (AFR) AF: 0.394 AC: 16299 AN: 41316

American (AMR) AF: 0.295 AC: 4464 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 674 AN: 3460

East Asian (EAS) AF: 0.226 AC: 1167 AN: 5172

South Asian (SAS) AF: 0.208 AC: 994 AN: 4788

European-Finnish (FIN) AF: 0.274 AC: 2882 AN: 10516

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14586 AN: 67908

Other (OTH) AF: 0.264 AC: 555 AN: 2100

Alfa AF: 0.248 Hom.: 2482

Bravo AF: 0.285

Asia WGS AF: 0.237 AC: 827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.68
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1246590; hg19: chr4-75098709;