rs1180242

Positions:

• chr6-83215836-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.1548+662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,142 control chromosomes in the GnomAD database, including 31,762 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 0.62 (31762 hom., cov: 33)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.1548+662A>G		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.1548+662A>G		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94229 AN: 152024 Hom.: 31699 Cov.: 33

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.620 AC: 94347 AN: 152142 Hom.: 31762 Cov.: 33 AF XY: 0.611 AC XY: 45431 AN XY: 74370

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.613

Alfa AF: 0.534 Hom.: 29413

Bravo AF: 0.647

Asia WGS AF: 0.480 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.42

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: rs1180242; hg19: chr6-83925555;