rs6922269

Variant names:

• chr6-150931849-G-A
• rs6922269
• NM_015440.5:c.1257-4955G>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.1257-4955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,038 control chromosomes in the GnomAD database, including 10,616 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 0.35 (10616 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 90 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.1257-4955G>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.1260-4955G>A		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.1062-4955G>A		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.1257-4955G>A		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.1260-4955G>A		intron	N/A	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.1251-4955G>A		intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52392 AN: 151920 Hom.: 10581 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.345 AC: 52491 AN: 152038 Hom.: 10616 Cov.: 31 AF XY: 0.343 AC XY: 25454 AN XY: 74318

African (AFR) AF: 0.559 AC: 23174 AN: 41464

American (AMR) AF: 0.370 AC: 5656 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5172

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10566

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.269 AC: 18256 AN: 67956

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.284 Hom.: 8680

Bravo AF: 0.362

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.55
PhyloP100		-0.43
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: rs6922269; hg19: chr6-151252985;