Genetic Variant ACSS2:c.1143+76G>T (chr20-34920785-G-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.1143+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,528,560 control chromosomes in the GnomAD database, including 282,696 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 0.55 ( 23366 hom., cov: 31)

Exomes 𝑓: 0.61 ( 259330 hom. )

Consequence

ACSS2
NM_018677.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.171

Publications

16 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 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.1143+76G>T	intron	N/A	NP_061147.1
ACSS2	NM_001076552.3		c.1182+76G>T	intron	N/A	NP_001070020.2
ACSS2	NM_001242393.2		c.858+76G>T	intron	N/A	NP_001229322.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.1143+76G>T	intron	N/A	ENSP00000353804.2
ACSS2	ENST00000253382.5	TSL:2	c.1182+76G>T	intron	N/A	ENSP00000253382.5
ACSS2	ENST00000476922.5	TSL:2	n.399-2538G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83018

AN:

151740

Hom.:

23355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.609

AC:

838850

AN:

1376702

Hom.:

259330

Cov.:

AF XY:

0.614

AC XY:

416891

AN XY:

679122

show subpopulations

African (AFR)

AF:

0.460

AC:

14319

AN:

31156

American (AMR)

AF:

0.304

AC:

10967

AN:

36092

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

13651

AN:

21546

East Asian (EAS)

AF:

0.441

AC:

17185

AN:

38944

South Asian (SAS)

AF:

0.742

AC:

56052

AN:

75522

European-Finnish (FIN)

AF:

0.604

AC:

29749

AN:

49286

Middle Eastern (MID)

AF:

0.623

AC:

2893

AN:

4646

European-Non Finnish (NFE)

AF:

0.621

AC:

659687

AN:

1062596

Other (OTH)

AF:

0.603

AC:

34347

AN:

56914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

16196

32392

48587

64783

80979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17926

35852

53778

71704

89630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

83038

AN:

151858

Hom.:

23366

Cov.:

AF XY:

0.546

AC XY:

40538

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.457

AC:

18933

AN:

41394

American (AMR)

AF:

0.425

AC:

6489

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2171

AN:

3470

East Asian (EAS)

AF:

0.449

AC:

2313

AN:

5148

South Asian (SAS)

AF:

0.735

AC:

3535

AN:

4808

European-Finnish (FIN)

AF:

0.596

AC:

6274

AN:

10534

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41581

AN:

67924

Other (OTH)

AF:

0.542

AC:

1141

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1859

3717

5576

7434

9293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.494

Hom.:

2521

Bravo

AF:

0.523

Asia WGS

AF:

0.596

AC:

2076

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.7

(source)

DANN

Benign

0.73

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over