chr6-83397515-C-T

Position:

• chr6-83397515-C-T

Variant summary

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

The NM_002395.6(ME1):​c.362+852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,030 control chromosomes in the GnomAD database, including 7,930 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 0.31 (7930 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME1	NM_002395.6	c.362+852G>A		intron_variant		ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.362+852G>A		intron_variant		1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47836 AN: 151912 Hom.: 7917 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.315 AC: 47866 AN: 152030 Hom.: 7930 Cov.: 32 AF XY: 0.311 AC XY: 23086 AN XY: 74312

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.362

Alfa AF: 0.316 Hom.: 1561

Bravo AF: 0.335

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.62

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: rs13215578; hg19: chr6-84107234; COSMIC: COSV63838152; COSMIC: COSV63838152;