rs12195069

chr6-150907876-G-Achr6-150907876-G-C

Variant summary

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

The NM_015440.5(MTHFD1L):c.892+2115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 151,236 control chromosomes in the GnomAD database, including 330 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 0.065 (330 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.892+2115G>A		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.892+2115G>A		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9864 AN: 151138 Hom.: 330 Cov.: 31

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0597

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

GnomAD4 genome AF: 0.0652 AC: 9867 AN: 151236 Hom.: 330 Cov.: 31 AF XY: 0.0628 AC XY: 4639 AN XY: 73888

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0658

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0677 Hom.: 505

Bravo AF: 0.0677

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.060
Dann	Benign	0.75

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: rs12195069; hg19: chr6-151229012;