rs1144188

Variant names:

• chr6-83274378-A-G
• rs1144188
• NM_002395.6:c.705-20640T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002395.6(ME1):​c.705-20640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,990 control chromosomes in the GnomAD database, including 7,413 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 0.30 (7413 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.705-20640T>C		intron_variant	Intron 6 of 13	ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.705-20640T>C		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44884 AN: 151872 Hom.: 7412 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.295 AC: 44894 AN: 151990 Hom.: 7413 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74310

African (AFR) AF: 0.156 AC: 6487 AN: 41452

American (AMR) AF: 0.391 AC: 5969 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1305 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1422 AN: 5178

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4816

European-Finnish (FIN) AF: 0.346 AC: 3656 AN: 10556

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23754 AN: 67938

Other (OTH) AF: 0.335 AC: 705 AN: 2106

Alfa AF: 0.277 Hom.: 2799

Bravo AF: 0.301

Asia WGS AF: 0.233 AC: 810 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1144188; hg19: chr6-83984097;