NM_001096.3:c.2643-106T>C

Variant names:

• chr17-41872288-A-G
• rs8071753
• NM_001096.3:c.2643-106T>C

Variant summary

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

The NM_001096.3(ACLY):​c.2643-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,095,206 control chromosomes in the GnomAD database, including 314,702 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 0.76 (44035 hom., cov: 31)
  • Exomes 𝑓: 0.76 (270667 hom.)
• Consequence: ACLY NM_001096.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 11 publications found

Genes affected

ACLY (HGNC:115): (ATP citrate lyase) ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACLY	NM_001096.3	c.2643-106T>C		intron_variant	Intron 23 of 28	ENST00000352035.7	NP_001087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACLY	ENST00000352035.7	c.2643-106T>C		intron_variant	Intron 23 of 28	1	NM_001096.3	ENSP00000253792.2

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115308 AN: 151942 Hom.: 44003 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.755 AC: 712364 AN: 943146 Hom.: 270667 AF XY: 0.759 AC XY: 360807 AN XY: 475164

African (AFR) AF: 0.710 AC: 16310 AN: 22984

American (AMR) AF: 0.876 AC: 28414 AN: 32450

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 16904 AN: 19486

East Asian (EAS) AF: 0.839 AC: 28659 AN: 34174

South Asian (SAS) AF: 0.826 AC: 52773 AN: 63890

European-Finnish (FIN) AF: 0.659 AC: 22722 AN: 34466

Middle Eastern (MID) AF: 0.822 AC: 3795 AN: 4618

European-Non Finnish (NFE) AF: 0.741 AC: 509841 AN: 687970

Other (OTH) AF: 0.764 AC: 32946 AN: 43108

GnomAD4 genome AF: 0.759 AC: 115387 AN: 152060 Hom.: 44035 Cov.: 31 AF XY: 0.757 AC XY: 56224 AN XY: 74310

African (AFR) AF: 0.727 AC: 30151 AN: 41460

American (AMR) AF: 0.846 AC: 12924 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3018 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4258 AN: 5176

South Asian (SAS) AF: 0.826 AC: 3987 AN: 4826

European-Finnish (FIN) AF: 0.628 AC: 6627 AN: 10554

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51780 AN: 67976

Other (OTH) AF: 0.782 AC: 1651 AN: 2110

Alfa AF: 0.775 Hom.: 8703

Bravo AF: 0.774

Asia WGS AF: 0.818 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.027
DANN	Benign	0.41
PhyloP100		-0.71
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: rs8071753; hg19: chr17-40028541; COSMIC: COSV61252453; COSMIC: COSV61252453;