6-150867555-T-C

Variant names:

• chr6-150867555-T-C
• rs2839947
• NM_015440.5:c.227+1506T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.97).
• 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 rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.227+1506T>C		intron_variant	Intron 1 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.227+1506T>C		intron_variant	Intron 1 of 27	1	NM_015440.5	ENSP00000356290.3

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

African (AFR) AF: 0.741 AC: 30710 AN: 41438

American (AMR) AF: 0.501 AC: 7636 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1584 AN: 3460

East Asian (EAS) AF: 0.426 AC: 2192 AN: 5144

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4824

European-Finnish (FIN) AF: 0.509 AC: 5359 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29544 AN: 67940

Other (OTH) AF: 0.503 AC: 1061 AN: 2110

Alfa AF: 0.460 Hom.: 12735

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
PhyloP100		-0.15
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: rs2839947; hg19: chr6-151188691;