rs7686861

chr4-74132767-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429335.5(MTHFD2L):c.-107+7250C>T variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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]

LOC105377277 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LOC105377277	XR_938878.2	n.69+5360G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD2L	ENST00000429335.5	c.-107+7250C>T		intron_variant, NMD_transcript_variant		1
MTHFD2L	ENST00000433372.5	n.80+7250C>T		intron_variant, non_coding_transcript_variant		1
MTHFD2L	ENST00000429519.5	n.458+7250C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.514

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7686861; hg19: chr4-74998484;