rs9371491

Variant names:

• chr6-151052519-A-T
• rs9371491
• NM_015440.5:c.2847+15402A>T

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2847+15402A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,134 control chromosomes in the GnomAD database, including 1,986 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 0.13 (1986 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2847+15402A>T		intron_variant	Intron 26 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2847+15402A>T		intron_variant	Intron 26 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2850+15402A>T		intron_variant	Intron 26 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.2652+15402A>T		intron_variant	Intron 26 of 27	5		ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19744 AN: 152016 Hom.: 1984 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.130 AC: 19754 AN: 152134 Hom.: 1986 Cov.: 32 AF XY: 0.131 AC XY: 9749 AN XY: 74354

African (AFR) AF: 0.0320 AC: 1330 AN: 41544

American (AMR) AF: 0.178 AC: 2715 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2779 AN: 5150

South Asian (SAS) AF: 0.140 AC: 674 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1504 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9936 AN: 67972

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.137 Hom.: 213

Bravo AF: 0.134

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.85
PhyloP100		0.098
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: rs9371491; hg19: chr6-151373655;