17-41872288-A-G

Position:

• chr17-41872288-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACLY	NM_001096.3	c.2643-106T>C		intron_variant		ENST00000352035.7	NP_001087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACLY	ENST00000352035.7	c.2643-106T>C		intron_variant		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

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.867

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.764

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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.782

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

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: rs8071753; hg19: chr17-40028541; COSMIC: COSV61252453; COSMIC: COSV61252453;