chr6-83307790-CTCTA-C

Variant names:

• chr6-83307790-CTCTA-C
• rs3839445
• NM_002395.6:c.704+7516_704+7519delTAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002395.6(ME1):​c.704+7516_704+7519delTAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,848 control chromosomes in the GnomAD database, including 6,054 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (6054 hom., cov: 30)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	NM_002395.6	MANE Select	c.704+7516_704+7519delTAGA		intron	N/A	NP_002386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	ENST00000369705.4	TSL:1 MANE Select	c.704+7516_704+7519delTAGA		intron	N/A	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27367 AN: 151728 Hom.: 6018 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.181 AC: 27463 AN: 151848 Hom.: 6054 Cov.: 30 AF XY: 0.178 AC XY: 13235 AN XY: 74254

African (AFR) AF: 0.527 AC: 21714 AN: 41232

American (AMR) AF: 0.101 AC: 1536 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.136 AC: 705 AN: 5174

South Asian (SAS) AF: 0.0850 AC: 409 AN: 4814

European-Finnish (FIN) AF: 0.0387 AC: 410 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2100 AN: 67980

Other (OTH) AF: 0.148 AC: 312 AN: 2112

Alfa AF: 0.119 Hom.: 462

Bravo AF: 0.201

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80
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: rs3839445; hg19: chr6-84017509;