6-150867555-T-C

Variant summary

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

The NM_015440.5(MTHFD1L):c.227+1506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,912 control chromosomes in the GnomAD database, including 22,934 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 0.53 (22934 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.227+1506T>C		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.227+1506T>C		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80641 AN: 151792 Hom.: 22889 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.532 AC: 80747 AN: 151912 Hom.: 22934 Cov.: 31 AF XY: 0.532 AC XY: 39515 AN XY: 74234

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.503

Alfa AF: 0.459 Hom.: 9433

Bravo AF: 0.545

Asia WGS AF: 0.446 AC: 1551 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	4.1
Dann	Benign	0.33

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: rs2839947; hg19: chr6-151188691;