rs1738567

Variant names:

• chr6-150968040-C-A
• rs1738567
• NM_015440.5:c.2013+3003C>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.2013+3003C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,220 control chromosomes in the GnomAD database, including 16,598 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 0.46 (16598 hom., cov: 29)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2013+3003C>A		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+3003C>A		intron_variant	Intron 19 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2016+3003C>A		intron_variant	Intron 19 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1818+3003C>A		intron_variant	Intron 19 of 27	5		ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68950 AN: 151100 Hom.: 16610 Cov.: 29

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.431

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.456 AC: 68956 AN: 151220 Hom.: 16598 Cov.: 29 AF XY: 0.457 AC XY: 33764 AN XY: 73864

African (AFR) AF: 0.330 AC: 13617 AN: 41272

American (AMR) AF: 0.358 AC: 5461 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1581 AN: 3452

East Asian (EAS) AF: 0.356 AC: 1815 AN: 5104

South Asian (SAS) AF: 0.556 AC: 2654 AN: 4774

European-Finnish (FIN) AF: 0.578 AC: 6041 AN: 10450

Middle Eastern (MID) AF: 0.411 AC: 116 AN: 282

European-Non Finnish (NFE) AF: 0.535 AC: 36220 AN: 67662

Other (OTH) AF: 0.442 AC: 926 AN: 2096

Alfa AF: 0.492 Hom.: 2375

Bravo AF: 0.435

Asia WGS AF: 0.422 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.82
PhyloP100		-1.3
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: rs1738567; hg19: chr6-151289176; COSMIC: COSV66227246; COSMIC: COSV66227246;