Genetic Variant NM_018677.4:c.1549-464A>G (chr20-34922859-A-G) – 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.1549-464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 157,766 control chromosomes in the GnomAD database, including 24,354 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 ( 23399 hom., cov: 32)

Exomes 𝑓: 0.55 ( 955 hom. )

Consequence

ACSS2
NM_018677.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

Publications

7 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=-0.72).

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.1549-464A>G		intron_variant	Intron 13 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.1549-464A>G		intron_variant	Intron 13 of 17	1	NM_018677.4	ENSP00000353804.2		Q9NR19-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83092

AN:

151828

Hom.:

23388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.737

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.550

AC:

3202

AN:

5820

Hom.:

955

Cov.:

AF XY:

0.559

AC XY:

1756

AN XY:

3144

show subpopulations

African (AFR)

AF:

0.322

AC:

AN:

American (AMR)

AF:

0.346

AC:

390

AN:

1126

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

AN:

East Asian (EAS)

AF:

0.455

AC:

265

AN:

582

South Asian (SAS)

AF:

0.727

AC:

413

AN:

568

European-Finnish (FIN)

AF:

0.581

AC:

AN:

136

Middle Eastern (MID)

AF:

0.875

AC:

AN:

European-Non Finnish (NFE)

AF:

0.608

AC:

1824

AN:

3002

Other (OTH)

AF:

0.631

AC:

140

AN:

222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

83112

AN:

151946

Hom.:

23399

Cov.:

AF XY:

0.547

AC XY:

40593

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.457

AC:

18946

AN:

41424

American (AMR)

AF:

0.424

AC:

6475

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2173

AN:

3472

East Asian (EAS)

AF:

0.450

AC:

2318

AN:

5150

South Asian (SAS)

AF:

0.736

AC:

3546

AN:

4820

European-Finnish (FIN)

AF:

0.596

AC:

6282

AN:

10540

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41629

AN:

67980

Other (OTH)

AF:

0.543

AC:

1143

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1924

3849

5773

7698

9622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.578

Hom.:

3874

Bravo

AF:

0.523

Asia WGS

AF:

0.596

AC:

2078

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.33

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