4-74295107-C-T

Variant names:

• chr4-74295107-C-T
• rs16850864
• NM_001144978.3:c.932-6590C>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.932-6590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,956 control chromosomes in the GnomAD database, including 2,860 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 0.12 (2860 hom., cov: 32)
• Consequence: MTHFD2L NM_001144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 9 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]

ENSG00000304732 (HGNC:58817):

LOC105377276 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 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.932-6590C>T		intron	N/A	NP_001138450.1	Q9H903-4
	MTHFD2L	NM_001004346.4		c.758-6590C>T		intron	N/A	NP_001004346.2	Q9H903-1
	MTHFD2L	NM_001351314.2		c.551-6590C>T		intron	N/A	NP_001338243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	ENST00000325278.7	TSL:5 MANE Select	c.932-6590C>T		intron	N/A	ENSP00000321984.7	Q9H903-4
	MTHFD2L	ENST00000461856.5	TSL:1	n.300-6590C>T		intron	N/A
	MTHFD2L	ENST00000465255.5	TSL:1	n.330-6590C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17948 AN: 151838 Hom.: 2844 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.00896

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.119 AC: 18020 AN: 151956 Hom.: 2860 Cov.: 32 AF XY: 0.117 AC XY: 8716 AN XY: 74278

African (AFR) AF: 0.363 AC: 14996 AN: 41366

American (AMR) AF: 0.0750 AC: 1143 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.0537 AC: 278 AN: 5174

South Asian (SAS) AF: 0.0797 AC: 384 AN: 4818

European-Finnish (FIN) AF: 0.00896 AC: 95 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 887 AN: 67974

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.0433 Hom.: 2607

Bravo AF: 0.134

Asia WGS AF: 0.103 AC: 357 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.46
PhyloP100		-0.36
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: rs16850864; hg19: chr4-75160824;