rs1144188

chr6-83274378-A-G

Variant summary

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

The NM_002395.6(ME1):c.705-20640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,990 control chromosomes in the GnomAD database, including 7,413 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 0.30 (7413 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.705-20640T>C		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.705-20640T>C		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44884 AN: 151872 Hom.: 7412 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.295 AC: 44894 AN: 151990 Hom.: 7413 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74310

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.335

Alfa AF: 0.305 Hom.: 1239

Bravo AF: 0.301

Asia WGS AF: 0.233 AC: 810 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.68

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: rs1144188; hg19: chr6-83984097;