rs17080689

Variant names:

• chr6-151006810-A-C
• rs17080689
• NM_015440.5:c.2126-3009A>C

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2126-3009A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,104 control chromosomes in the GnomAD database, including 1,269 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 0.12 (1269 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2126-3009A>C		intron_variant	Intron 20 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2126-3009A>C		intron_variant	Intron 20 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2129-3009A>C		intron_variant	Intron 20 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1931-3009A>C		intron_variant	Intron 20 of 27	5		ENSP00000479539.1
MTHFD1L	ENST00000478643.1	n.282-3009A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17997 AN: 151986 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.118 AC: 18014 AN: 152104 Hom.: 1269 Cov.: 32 AF XY: 0.114 AC XY: 8515 AN XY: 74382

African (AFR) AF: 0.182 AC: 7555 AN: 41410

American (AMR) AF: 0.0733 AC: 1121 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3472

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5176

South Asian (SAS) AF: 0.0896 AC: 432 AN: 4820

European-Finnish (FIN) AF: 0.0910 AC: 965 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6898 AN: 68012

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.106 Hom.: 1700

Bravo AF: 0.121

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.28
PhyloP100		-0.20
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: rs17080689; hg19: chr6-151327946;