rs10014791

Variant names:

• chr4-74279749-A-G
• rs10014791
• NM_001144978.3:c.806-1676A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144978.3(MTHFD2L):​c.806-1676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,144 control chromosomes in the GnomAD database, including 628 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 0.060 (628 hom., cov: 32)
• Consequence: MTHFD2L NM_001144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 3 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 = 0.158 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	NM_001144978.3	MANE Select	c.806-1676A>G		intron	N/A	NP_001138450.1
	MTHFD2L	NM_001004346.4		c.632-1676A>G		intron	N/A	NP_001004346.2
	MTHFD2L	NM_001351314.2		c.425-1676A>G		intron	N/A	NP_001338243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	ENST00000325278.7	TSL:5 MANE Select	c.806-1676A>G		intron	N/A	ENSP00000321984.7
	MTHFD2L	ENST00000461856.5	TSL:1	n.174-1676A>G		intron	N/A
	MTHFD2L	ENST00000395759.6	TSL:5	c.806-1676A>G		intron	N/A	ENSP00000379108.2

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9080 AN: 152026 Hom.: 623 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0600 AC: 9122 AN: 152144 Hom.: 628 Cov.: 32 AF XY: 0.0598 AC XY: 4449 AN XY: 74404

African (AFR) AF: 0.161 AC: 6690 AN: 41494

American (AMR) AF: 0.0473 AC: 723 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.0532 AC: 275 AN: 5168

South Asian (SAS) AF: 0.0776 AC: 374 AN: 4818

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 820 AN: 67986

Other (OTH) AF: 0.0573 AC: 121 AN: 2110

Alfa AF: 0.0295 Hom.: 238

Bravo AF: 0.0664

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.61
PhyloP100		-0.67
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: rs10014791; hg19: chr4-75145466;