rs1145913

Variant names:

• chr6-83284209-A-C
• rs1145913
• NM_002395.6:c.705-30471T>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.705-30471T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,906 control chromosomes in the GnomAD database, including 9,623 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 (9623 hom., cov: 31)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.705-30471T>G		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.705-30471T>G		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53425 AN: 151788 Hom.: 9617 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.352 AC: 53456 AN: 151906 Hom.: 9623 Cov.: 31 AF XY: 0.348 AC XY: 25812 AN XY: 74222

African (AFR) AF: 0.353 AC: 14635 AN: 41420

American (AMR) AF: 0.410 AC: 6251 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3464

East Asian (EAS) AF: 0.274 AC: 1418 AN: 5174

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4812

European-Finnish (FIN) AF: 0.346 AC: 3648 AN: 10538

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23796 AN: 67922

Other (OTH) AF: 0.373 AC: 788 AN: 2112

Alfa AF: 0.342 Hom.: 1144

Bravo AF: 0.365

Asia WGS AF: 0.248 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.89
PhyloP100		-1.0
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: rs1145913; hg19: chr6-83993928;