rs1144184

Positions:

• chr6-83308202-T-C

Variant summary

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

The NM_002395.6(ME1):​c.704+7108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,914 control chromosomes in the GnomAD database, including 19,230 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 (19230 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME1	NM_002395.6	c.704+7108A>G		intron_variant		ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.704+7108A>G		intron_variant		1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72891 AN: 151796 Hom.: 19188 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.480 AC: 72989 AN: 151914 Hom.: 19230 Cov.: 32 AF XY: 0.477 AC XY: 35366 AN XY: 74216

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.492

Alfa AF: 0.397 Hom.: 24676

Bravo AF: 0.508

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.34

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: rs1144184; hg19: chr6-84017921;