chr6-150889871-A-G

Variant names:

• chr6-150889871-A-G
• rs13201018
• NM_015440.5:c.780+1890A>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.780+1890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 152,202 control chromosomes in the GnomAD database, including 389 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 0.064 (389 hom., cov: 33)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.780+1890A>G		intron_variant	Intron 7 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.780+1890A>G		intron_variant	Intron 7 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9795 AN: 152084 Hom.: 389 Cov.: 33

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0644 AC: 9796 AN: 152202 Hom.: 389 Cov.: 33 AF XY: 0.0629 AC XY: 4681 AN XY: 74416

African (AFR) AF: 0.0340 AC: 1414 AN: 41534

American (AMR) AF: 0.0697 AC: 1066 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4822

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0846 AC: 5749 AN: 67992

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0776 Hom.: 245

Bravo AF: 0.0626

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-0.43
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: rs13201018; hg19: chr6-151211007;