6-150883407-A-G

Variant names:

• chr6-150883407-A-G
• rs7765521
• NM_015440.5:c.542+521A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):​c.542+521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,974 control chromosomes in the GnomAD database, including 23,369 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 0.55 (23369 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.542+521A>G		intron_variant	Intron 5 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.542+521A>G		intron_variant	Intron 5 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83599 AN: 151856 Hom.: 23332 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.551 AC: 83696 AN: 151974 Hom.: 23369 Cov.: 31 AF XY: 0.550 AC XY: 40849 AN XY: 74268

African (AFR) AF: 0.627 AC: 25976 AN: 41436

American (AMR) AF: 0.574 AC: 8771 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2267 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2114 AN: 4808

European-Finnish (FIN) AF: 0.553 AC: 5831 AN: 10536

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35052 AN: 67970

Other (OTH) AF: 0.545 AC: 1151 AN: 2110

Alfa AF: 0.533 Hom.: 8520

Bravo AF: 0.559

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		0.16
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: rs7765521; hg19: chr6-151204543; COSMIC: COSV107468772;