rs1145908

Variant names:

• chr6-83304679-A-G
• rs1145908
• NM_002395.6:c.704+10631T>C

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+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
• Publications: 3 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=-0.86).
• 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 rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.704+10631T>C		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+10631T>C		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

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

African (AFR) AF: 0.353 AC: 14664 AN: 41486

American (AMR) AF: 0.408 AC: 6233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1415 AN: 5172

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4824

European-Finnish (FIN) AF: 0.346 AC: 3656 AN: 10578

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23703 AN: 67968

Other (OTH) AF: 0.370 AC: 781 AN: 2108

Alfa AF: 0.340 Hom.: 1233

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
PhyloP100		0.083
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: rs1145908; hg19: chr6-84014398;