rs1738574

Variant names:

• chr6-150965834-A-G
• rs1738574
• NM_015440.5:c.2013+797A>G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2013+797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,982 control chromosomes in the GnomAD database, including 17,915 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 0.47 (17915 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2013+797A>G		intron_variant	Intron 19 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2013+797A>G		intron_variant	Intron 19 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2016+797A>G		intron_variant	Intron 19 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1818+797A>G		intron_variant	Intron 19 of 27	5		ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71837 AN: 151864 Hom.: 17928 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.473 AC: 71846 AN: 151982 Hom.: 17915 Cov.: 32 AF XY: 0.473 AC XY: 35168 AN XY: 74294

African (AFR) AF: 0.345 AC: 14302 AN: 41456

American (AMR) AF: 0.372 AC: 5677 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1643 AN: 3462

East Asian (EAS) AF: 0.372 AC: 1925 AN: 5176

South Asian (SAS) AF: 0.593 AC: 2853 AN: 4808

European-Finnish (FIN) AF: 0.586 AC: 6180 AN: 10542

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37625 AN: 67960

Other (OTH) AF: 0.461 AC: 970 AN: 2102

Alfa AF: 0.488 Hom.: 2828

Bravo AF: 0.451

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.098
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: rs1738574; hg19: chr6-151286970; COSMIC: COSV66227232;