rs2295083

Positions:

• chr6-150904429-G-A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.781-1221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,056 control chromosomes in the GnomAD database, including 2,949 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 0.19 (2949 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.781-1221G>A		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.781-1221G>A		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29575 AN: 151938 Hom.: 2939 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.195 AC: 29607 AN: 152056 Hom.: 2949 Cov.: 32 AF XY: 0.194 AC XY: 14410 AN XY: 74306

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.195

Alfa AF: 0.187 Hom.: 631

Bravo AF: 0.193

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.81

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: rs2295083; hg19: chr6-151225565;