rs1555179

Positions:

• chr6-150950220-G-A

Variant summary

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

The ENST00000367321.8(MTHFD1L):​c.1726+1087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,908 control chromosomes in the GnomAD database, including 7,587 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 0.30 (7587 hom., cov: 32)
• Consequence: MTHFD1L ENST00000367321.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.1726+1087G>A		intron_variant		ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1726+1087G>A		intron_variant		1	NM_015440.5	ENSP00000356290	P4
MTHFD1L	ENST00000611279.4	c.1729+1087G>A		intron_variant		5		ENSP00000478253	A1
MTHFD1L	ENST00000618312.4	c.1531+1087G>A		intron_variant		5		ENSP00000479539

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46153 AN: 151788 Hom.: 7579 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.304 AC: 46195 AN: 151908 Hom.: 7587 Cov.: 32 AF XY: 0.305 AC XY: 22665 AN XY: 74232

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.315

Alfa AF: 0.335 Hom.: 17861

Bravo AF: 0.295

Asia WGS AF: 0.333 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.46

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: rs1555179; hg19: chr6-151271356; COSMIC: COSV66227195;