Genetic Variant NM_018677.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS2	NM_018677.4 link	c.1143+76G>T		intron_variant	Intron 9 of 17	ENST00000360596.7	NP_061147.1	Q9NR19-1Q6DKJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS2	ENST00000360596.7 link	c.1143+76G>T		intron_variant	Intron 9 of 17	1	NM_018677.4	ENSP00000353804.2		Q9NR19-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over