rs1170347

Variant names:

• chr6-83311575-G-A
• rs1170347
• NM_002395.6:c.704+3735C>T

Variant summary

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

The NM_002395.6(ME1):​c.704+3735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,922 control chromosomes in the GnomAD database, including 5,596 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 0.25 (5596 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.704+3735C>T		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.704+3735C>T		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38619 AN: 151804 Hom.: 5592 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.254 AC: 38619 AN: 151922 Hom.: 5596 Cov.: 32 AF XY: 0.249 AC XY: 18517 AN XY: 74248

African (AFR) AF: 0.134 AC: 5561 AN: 41446

American (AMR) AF: 0.353 AC: 5382 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.109 AC: 562 AN: 5174

South Asian (SAS) AF: 0.152 AC: 735 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2911 AN: 10526

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20975 AN: 67926

Other (OTH) AF: 0.298 AC: 628 AN: 2110

Alfa AF: 0.260 Hom.: 733

Bravo AF: 0.262

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.40
PhyloP100		0.47
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: rs1170347; hg19: chr6-84021294;