chr6-83279267-G-T

Variant names:

• chr6-83279267-G-T
• rs1145916
• NM_002395.6:c.705-25529C>A

Variant summary

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

The NM_002395.6(ME1):​c.705-25529C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,962 control chromosomes in the GnomAD database, including 19,992 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 0.49 (19992 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.705-25529C>A		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.705-25529C>A		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74273 AN: 151844 Hom.: 19943 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.489 AC: 74378 AN: 151962 Hom.: 19992 Cov.: 32 AF XY: 0.484 AC XY: 35953 AN XY: 74266

African (AFR) AF: 0.722 AC: 29938 AN: 41438

American (AMR) AF: 0.498 AC: 7607 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2119 AN: 5158

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4078 AN: 10548

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25970 AN: 67950

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.446 Hom.: 2176

Bravo AF: 0.515

Asia WGS AF: 0.385 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.43
PhyloP100		0.0080
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: rs1145916; hg19: chr6-83988986; COSMIC: COSV63840448;