rs1144185

chr6-83302900-A-Gchr6-83302900-A-T

Variant summary

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

The NM_002395.6(ME1):c.704+12410T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,986 control chromosomes in the GnomAD database, including 9,733 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 (9733 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.704+12410T>C		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.704+12410T>C		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53730 AN: 151870 Hom.: 9727 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.354 AC: 53761 AN: 151986 Hom.: 9733 Cov.: 32 AF XY: 0.349 AC XY: 25963 AN XY: 74302

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.376

Alfa AF: 0.345 Hom.: 5028

Bravo AF: 0.368

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.62
Dann	Benign	0.57

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: rs1144185; hg19: chr6-84012619;