rs6941094

Positions:

• chr6-83428766-C-A

Variant summary

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

The NM_002395.6(ME1):​c.78+2111G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,880 control chromosomes in the GnomAD database, including 9,811 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 0.35 (9811 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.78+2111G>T		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.78+2111G>T		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53474 AN: 151762 Hom.: 9798 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.352 AC: 53515 AN: 151880 Hom.: 9811 Cov.: 32 AF XY: 0.347 AC XY: 25740 AN XY: 74222

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.389

Alfa AF: 0.334 Hom.: 12694

Bravo AF: 0.377

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.40

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: rs6941094; hg19: chr6-84138485;