rs1180237

chr6-83234209-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002395.6(ME1):c.1026+3508T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,890 control chromosomes in the GnomAD database, including 15,686 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 0.45 (15686 hom., cov: 31)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

ME1 (HGNC:6983): (malic enzyme 1) This gene encodes a cytosolic, NADP-dependent enzyme that generates NADPH for fatty acid biosynthesis. The activity of this enzyme, the reversible oxidative decarboxylation of malate, links the glycolytic and citric acid cycles. The regulation of expression for this gene is complex. Increased expression can result from elevated levels of thyroid hormones or by higher proportions of carbohydrates in the diet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.1026+3508T>G		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.1026+3508T>G		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67701 AN: 151772 Hom.: 15659 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.446 AC: 67770 AN: 151890 Hom.: 15686 Cov.: 31 AF XY: 0.441 AC XY: 32727 AN XY: 74242

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.451

Alfa AF: 0.416 Hom.: 21628

Bravo AF: 0.463

Asia WGS AF: 0.334 AC: 1166 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	7.1
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1180237; hg19: chr6-83943928; COSMIC: COSV63842469;