rs1145908

chr6-83304679-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002395.6(ME1):c.704+10631T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,080 control chromosomes in the GnomAD database, including 9,598 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 (9598 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.704+10631T>C		intron_variant		ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.704+10631T>C		intron_variant		1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53343 AN: 151962 Hom.: 9592 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.408

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: 0.349

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.351 AC: 53374 AN: 152080 Hom.: 9598 Cov.: 32 AF XY: 0.347 AC XY: 25768 AN XY: 74338

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.370

Alfa AF: 0.341 Hom.: 1192

Bravo AF: 0.364

Asia WGS AF: 0.247 AC: 861 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1145908; hg19: chr6-84014398;