rs487637

Variant names:

• chr6-151018306-C-A
• rs487637
• NM_015440.5:c.2586+2613C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151018306-C-A
• chr6-151018306-C-G
• chr6-151018306-C-T

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2586+2613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,188 control chromosomes in the GnomAD database, including 48,951 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 0.80 (48951 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

Genes affected

MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2586+2613C>A		intron_variant	Intron 24 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2586+2613C>A		intron_variant	Intron 24 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2589+2613C>A		intron_variant	Intron 24 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.2391+2613C>A		intron_variant	Intron 24 of 27	5		ENSP00000479539.1
MTHFD1L	ENST00000420192.1	c.279+2613C>A		intron_variant	Intron 2 of 2	2		ENSP00000395158.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120886 AN: 152068 Hom.: 48902 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.795 AC: 120996 AN: 152188 Hom.: 48951 Cov.: 33 AF XY: 0.796 AC XY: 59244 AN XY: 74388

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.784

Alfa AF: 0.724 Hom.: 52298

Bravo AF: 0.803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.91
DANN	Benign	0.70

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: rs487637; hg19: chr6-151339442;