rs11155772

Variant names:

• chr6-151073426-G-T
• rs11155772
• NM_015440.5:c.2848-19041G>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.2848-19041G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,000 control chromosomes in the GnomAD database, including 5,595 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 0.27 (5595 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.2848-19041G>T		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.2851-19041G>T		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.2653-19041G>T		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.2848-19041G>T		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.2851-19041G>T		intron	N/A	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.2842-19041G>T		intron	N/A	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40673 AN: 151882 Hom.: 5590 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.268 AC: 40700 AN: 152000 Hom.: 5595 Cov.: 32 AF XY: 0.271 AC XY: 20152 AN XY: 74300

African (AFR) AF: 0.273 AC: 11309 AN: 41452

American (AMR) AF: 0.232 AC: 3536 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5158

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4812

European-Finnish (FIN) AF: 0.302 AC: 3188 AN: 10554

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17991 AN: 67972

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.260 Hom.: 1724

Bravo AF: 0.255

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.64
PhyloP100		-1.3
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: rs11155772; hg19: chr6-151394562;