rs1180242

Variant names:

• chr6-83215836-T-C
• rs1180242
• NM_002395.6:c.1548+662A>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.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
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.1548+662A>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.1548+662A>G		intron	N/A	ENSP00000358719.3	P48163-1
	ME1	ENST00000956348.1		c.1662+662A>G		intron	N/A	ENSP00000626407.1
	ME1	ENST00000956344.1		c.1602+662A>G		intron	N/A	ENSP00000626403.1

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

African (AFR) AF: 0.907 AC: 37668 AN: 41544

American (AMR) AF: 0.597 AC: 9119 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1921 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2341 AN: 5150

South Asian (SAS) AF: 0.430 AC: 2074 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4871 AN: 10578

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34446 AN: 67988

Other (OTH) AF: 0.613 AC: 1295 AN: 2114

Alfa AF: 0.546 Hom.: 39134

Bravo AF: 0.647

Asia WGS AF: 0.480 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		-1.7
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: rs1180242; hg19: chr6-83925555;