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GeneBe

17-41878178-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001096.3(ACLY):c.2412C>T(p.Leu804=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,593,960 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

ACLY
NM_001096.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-41878178-G-A is Benign according to our data. Variant chr17-41878178-G-A is described in ClinVar as [Benign]. Clinvar id is 788605.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.4 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 259 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACLYNM_001096.3 linkuse as main transcriptc.2412C>T p.Leu804= synonymous_variant 22/29 ENST00000352035.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACLYENST00000352035.7 linkuse as main transcriptc.2412C>T p.Leu804= synonymous_variant 22/291 NM_001096.3 P3P53396-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00170
AC:
259
AN:
152080
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00585
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000918
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000396
AC:
92
AN:
232136
Hom.:
0
AF XY:
0.000364
AC XY:
46
AN XY:
126524
show subpopulations
Gnomad AFR exome
AF:
0.00544
Gnomad AMR exome
AF:
0.000161
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000708
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000283
Gnomad OTH exome
AF:
0.000367
GnomAD4 exome
AF:
0.000150
AC:
216
AN:
1441762
Hom.:
1
Cov.:
30
AF XY:
0.000142
AC XY:
102
AN XY:
717458
show subpopulations
Gnomad4 AFR exome
AF:
0.00516
Gnomad4 AMR exome
AF:
0.000239
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000531
Gnomad4 SAS exome
AF:
0.0000239
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000998
Gnomad4 OTH exome
AF:
0.000438
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00171
AC:
260
AN:
152198
Hom.:
1
Cov.:
31
AF XY:
0.00187
AC XY:
139
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.00585
Gnomad4 AMR
AF:
0.000917
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000636
Hom.:
1
Bravo
AF:
0.00202

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
0.29
Dann
Benign
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35022178; hg19: chr17-40034431; COSMIC: COSV61253004; API