rs1144193

chr6-83269315-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.705-15577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,820 control chromosomes in the GnomAD database, including 18,767 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 0.48 (18767 hom., cov: 31)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933

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 = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.705-15577T>C		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.705-15577T>C		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72059 AN: 151710 Hom.: 18733 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.475 AC: 72143 AN: 151820 Hom.: 18767 Cov.: 31 AF XY: 0.471 AC XY: 34912 AN XY: 74152

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.480

Alfa AF: 0.422 Hom.: 1825

Bravo AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.28
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: rs1144193; hg19: chr6-83979034;