rs10014791

Positions:

• chr4-74279749-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105377276 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD2L	NM_001144978.3	c.806-1676A>G		intron_variant		ENST00000325278.7
LOC105377276	XR_938877.3	n.273-971T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD2L	ENST00000325278.7	c.806-1676A>G		intron_variant		5	NM_001144978.3	P1

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.0776

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0231 Hom.: 120

Bravo AF: 0.0664

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.61

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: rs10014791; hg19: chr4-75145466;