rs1180243

chr6-83213997-G-T

Variant summary

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

The NM_002395.6(ME1):c.1549-1903C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,922 control chromosomes in the GnomAD database, including 20,531 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 0.50 (20531 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.1549-1903C>A		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.1549-1903C>A		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75959 AN: 151804 Hom.: 20489 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.501 AC: 76060 AN: 151922 Hom.: 20531 Cov.: 32 AF XY: 0.496 AC XY: 36863 AN XY: 74272

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.482

Alfa AF: 0.432 Hom.: 6557

Bravo AF: 0.521

Asia WGS AF: 0.388 AC: 1348 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.4
Dann	Benign	0.45

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: rs1180243; hg19: chr6-83923716;