chr6-151060741-G-A

Variant names:

• chr6-151060741-G-A
• rs6913898
• NM_015440.5:c.2847+23624G>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.2847+23624G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,064 control chromosomes in the GnomAD database, including 20,952 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 0.52 (20952 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.2847+23624G>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2850+23624G>A		intron	N/A	NP_001229696.1
	MTHFD1L	NM_001242768.2		c.2652+23624G>A		intron	N/A	NP_001229697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.2847+23624G>A		intron	N/A	ENSP00000356290.3
	MTHFD1L	ENST00000611279.4	TSL:5	c.2850+23624G>A		intron	N/A	ENSP00000478253.1
	MTHFD1L	ENST00000618312.4	TSL:5	c.2652+23624G>A		intron	N/A	ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79401 AN: 151946 Hom.: 20947 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.523 AC: 79455 AN: 152064 Hom.: 20952 Cov.: 33 AF XY: 0.517 AC XY: 38451 AN XY: 74310

African (AFR) AF: 0.558 AC: 23169 AN: 41490

American (AMR) AF: 0.556 AC: 8501 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1923 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2873 AN: 5150

South Asian (SAS) AF: 0.414 AC: 1996 AN: 4824

European-Finnish (FIN) AF: 0.442 AC: 4668 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34489 AN: 67976

Other (OTH) AF: 0.532 AC: 1123 AN: 2112

Alfa AF: 0.510 Hom.: 11448

Bravo AF: 0.541

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.076
DANN	Benign	0.63
PhyloP100		-1.9
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: rs6913898; hg19: chr6-151381877;