rs17080476

Variant names:

• chr6-150908861-A-G
• rs17080476
• NM_015440.5:c.892+3100A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-150908861-A-G
• chr6-150908861-A-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.892+3100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,946 control chromosomes in the GnomAD database, including 2,519 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 0.17 (2519 hom., cov: 30)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.892+3100A>G		intron_variant	Intron 8 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.892+3100A>G		intron_variant	Intron 8 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25130 AN: 151828 Hom.: 2510 Cov.: 30

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.166 AC: 25152 AN: 151946 Hom.: 2519 Cov.: 30 AF XY: 0.172 AC XY: 12765 AN XY: 74242

African (AFR) AF: 0.0611 AC: 2536 AN: 41496

American (AMR) AF: 0.214 AC: 3267 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1493 AN: 5154

South Asian (SAS) AF: 0.297 AC: 1426 AN: 4806

European-Finnish (FIN) AF: 0.248 AC: 2605 AN: 10518

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12631 AN: 67950

Other (OTH) AF: 0.165 AC: 348 AN: 2104

Alfa AF: 0.176 Hom.: 3226

Bravo AF: 0.156

Asia WGS AF: 0.285 AC: 988 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		0.45
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: rs17080476; hg19: chr6-151229997;