Genetic Variant ACSS2:c.*771A>T (chr20-34927985-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018677.4(ACSS2):c.*771A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,812 control chromosomes in the GnomAD database, including 308 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 0.059 ( 307 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1 hom. )

Consequence

ACSS2
NM_018677.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223

Publications

11 publications found

Variant links:

Genes affected

ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACSS2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACSS2	NM_018677.4	MANE Select	c.*771A>T	downstream_gene	N/A	NP_061147.1
ACSS2	NM_001076552.3		c.*771A>T	downstream_gene	N/A	NP_001070020.2
ACSS2	NM_001242393.2		c.*771A>T	downstream_gene	N/A	NP_001229322.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.*771A>T	downstream_gene	N/A	ENSP00000353804.2
ACSS2	ENST00000253382.5	TSL:2	c.*771A>T	downstream_gene	N/A	ENSP00000253382.5
ACSS2	ENST00000476922.5	TSL:2	n.*23A>T	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9022

AN:

152058

Hom.:

305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.0789

Gnomad EAS

AF:

0.0801

Gnomad SAS

AF:

0.0621

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.0545

GnomAD4 exome

AF:

0.0442

AC:

AN:

634

Hom.:

Cov.:

AF XY:

0.0419

AC XY:

AN XY:

358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0824

AC:

AN:

182

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0351

AC:

AN:

370

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0593

AC:

9026

AN:

152178

Hom.:

307

Cov.:

AF XY:

0.0609

AC XY:

4530

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0428

AC:

1778

AN:

41526

American (AMR)

AF:

0.0456

AC:

697

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0789

AC:

274

AN:

3472

East Asian (EAS)

AF:

0.0794

AC:

411

AN:

5174

South Asian (SAS)

AF:

0.0634

AC:

305

AN:

4812

European-Finnish (FIN)

AF:

0.0871

AC:

922

AN:

10586

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4448

AN:

67996

Other (OTH)

AF:

0.0573

AC:

121

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

441

882

1323

1764

2205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0288

Hom.:

Bravo

AF:

0.0555

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.2

(source)

DANN

Benign

0.71

PhyloP100

0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over