rs7686861

Variant names:

• chr4-74132767-C-T
• rs7686861
• ENST00000429335.5:n.-107+7250C>T

Variant summary

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

The ENST00000429335.5(MTHFD2L):​n.-107+7250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,018 control chromosomes in the GnomAD database, including 20,712 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 0.48 (20712 hom., cov: 32)
• Consequence: MTHFD2L ENST00000429335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 5 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]

ENSG00000304759 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD2L	NM_001351310.2	c.-66+7250C>T		intron_variant	Intron 2 of 8		NP_001338239.1
MTHFD2L	NM_001351311.2	c.-32+7250C>T		intron_variant	Intron 2 of 7		NP_001338240.1
MTHFD2L	XM_017008218.3	c.-3831+7250C>T		intron_variant	Intron 3 of 12		XP_016863707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD2L	ENST00000429335.5	n.-107+7250C>T		intron_variant	Intron 2 of 6	1		ENSP00000409391.1
MTHFD2L	ENST00000433372.5	n.80+7250C>T		intron_variant	Intron 1 of 7	1
MTHFD2L	ENST00000429519.5	n.458+7250C>T		intron_variant	Intron 3 of 9	5

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73108 AN: 151900 Hom.: 20713 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.481 AC: 73108 AN: 152018 Hom.: 20712 Cov.: 32 AF XY: 0.486 AC XY: 36140 AN XY: 74296

African (AFR) AF: 0.166 AC: 6897 AN: 41494

American (AMR) AF: 0.621 AC: 9486 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1721 AN: 5176

South Asian (SAS) AF: 0.545 AC: 2623 AN: 4810

European-Finnish (FIN) AF: 0.664 AC: 7009 AN: 10550

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41503 AN: 67930

Other (OTH) AF: 0.514 AC: 1086 AN: 2114

Alfa AF: 0.546 Hom.: 3739

Bravo AF: 0.465

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.75
DANN	Benign	0.28
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7686861; hg19: chr4-74998484;