rs6922269

Positions:

• chr6-150931849-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367321.8(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 ENST00000367321.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.1257-4955G>A		intron_variant		ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1257-4955G>A		intron_variant		1	NM_015440.5	ENSP00000356290	P4
MTHFD1L	ENST00000611279.4	c.1260-4955G>A		intron_variant		5		ENSP00000478253	A1
MTHFD1L	ENST00000618312.4	c.1062-4955G>A		intron_variant		5		ENSP00000479539
MTHFD1L	ENST00000441122.5	c.*463-4955G>A		intron_variant, NMD_transcript_variant		5		ENSP00000407070

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

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.325

Alfa AF: 0.272 Hom.: 5510

Bravo AF: 0.362

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs6922269; hg19: chr6-151252985;