rs1555179

Variant names:

• chr6-150950220-G-A
• rs1555179
• NM_015440.5:c.1726+1087G>A

Variant summary

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

The NM_015440.5(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 NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.1726+1087G>A		intron_variant	Intron 16 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1726+1087G>A		intron_variant	Intron 16 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.1729+1087G>A		intron_variant	Intron 16 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1531+1087G>A		intron_variant	Intron 16 of 27	5		ENSP00000479539.1

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

African (AFR) AF: 0.187 AC: 7748 AN: 41444

American (AMR) AF: 0.333 AC: 5085 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2390 AN: 5136

South Asian (SAS) AF: 0.260 AC: 1249 AN: 4810

European-Finnish (FIN) AF: 0.398 AC: 4197 AN: 10544

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23514 AN: 67942

Other (OTH) AF: 0.315 AC: 664 AN: 2106

Alfa AF: 0.333 Hom.: 37009

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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