rs1180186

chr6-83259227-T-G

Variant summary

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

The NM_002395.6(ME1):c.705-5489A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,974 control chromosomes in the GnomAD database, including 18,020 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 0.47 (18020 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.705-5489A>C		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.705-5489A>C		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71855 AN: 151854 Hom.: 17982 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.473 AC: 71947 AN: 151974 Hom.: 18020 Cov.: 32 AF XY: 0.468 AC XY: 34769 AN XY: 74256

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.468

Alfa AF: 0.417 Hom.: 9906

Bravo AF: 0.492

Asia WGS AF: 0.373 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.9
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: rs1180186; hg19: chr6-83968946;