rs1180237

Variant names:

• chr6-83234209-A-C
• rs1180237
• NM_002395.6:c.1026+3508T>G

Variant summary

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

The NM_002395.6(ME1):​c.1026+3508T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,890 control chromosomes in the GnomAD database, including 15,686 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 0.45 (15686 hom., cov: 31)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002395.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	NM_002395.6	MANE Select	c.1026+3508T>G		intron	N/A	NP_002386.1	P48163-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	ENST00000369705.4	TSL:1 MANE Select	c.1026+3508T>G		intron	N/A	ENSP00000358719.3	P48163-1
	ME1	ENST00000956348.1		c.1140+3508T>G		intron	N/A	ENSP00000626407.1
	ME1	ENST00000956344.1		c.1080+3508T>G		intron	N/A	ENSP00000626403.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67701 AN: 151772 Hom.: 15659 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.446 AC: 67770 AN: 151890 Hom.: 15686 Cov.: 31 AF XY: 0.441 AC XY: 32727 AN XY: 74242

African (AFR) AF: 0.560 AC: 23194 AN: 41408

American (AMR) AF: 0.462 AC: 7047 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.342 AC: 1766 AN: 5160

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4129 AN: 10534

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27409 AN: 67948

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.423 Hom.: 35864

Bravo AF: 0.463

Asia WGS AF: 0.334 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		-0.092
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1180237;

hg19: chr6-83943928;

COSMIC: COSV63842469;