chr17-41872288-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001096.3(ACLY):​c.2643-106T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 946654 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 476844

African (AFR) AF: 0.00 AC: 0 AN: 23066

American (AMR) AF: 0.00 AC: 0 AN: 32476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19512

East Asian (EAS) AF: 0.00 AC: 0 AN: 34194

South Asian (SAS) AF: 0.00 AC: 0 AN: 63996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 691008

Other (OTH) AF: 0.00 AC: 0 AN: 43244

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.022
DANN	Benign	0.52
PhyloP100		-0.71

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;