rs1180243

Variant names:

• chr6-83213997-G-T
• rs1180243
• NM_002395.6:c.1549-1903C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.1549-1903C>A		intron_variant	Intron 13 of 13	ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.1549-1903C>A		intron_variant	Intron 13 of 13	1	NM_002395.6	ENSP00000358719.3

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

African (AFR) AF: 0.717 AC: 29723 AN: 41448

American (AMR) AF: 0.493 AC: 7515 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2068 AN: 5152

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4816

European-Finnish (FIN) AF: 0.406 AC: 4274 AN: 10534

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27832 AN: 67944

Other (OTH) AF: 0.482 AC: 1017 AN: 2112

Alfa AF: 0.431 Hom.: 7275

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
PhyloP100		0.89
Mutation Taster		=17/83	disease causing

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: rs1180243; hg19: chr6-83923716;