Genetic Variant ACADSB:c.203-1093A>G (chr10-123036654-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_001609.4(ACADSB):c.203-1093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,240 control chromosomes in the GnomAD database, including 948 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 0.10 ( 948 hom., cov: 33)

Consequence

ACADSB
NM_001609.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.232

Publications

3 publications found

Variant links:

Genes affected

ACADSB (HGNC:91): (acyl-CoA dehydrogenase short/branched chain) Short/branched chain acyl-CoA dehydrogenase(ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The cDNA encodes for a mitochondrial precursor protein which is cleaved upon mitochondrial import and predicted to yield a mature peptide of approximately 43.7-KDa. [provided by RefSeq, Jul 2008]

ACADSB Gene-Disease associations (from GenCC):

2-methylbutyryl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACADSB links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADSB	NM_001609.4 link	c.203-1093A>G		intron_variant	Intron 2 of 10	ENST00000358776.7	NP_001600.1
ACADSB	NM_001330174.3 link	c.-4+2139A>G		intron_variant	Intron 2 of 9		NP_001317103.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ACADSB	ENST00000358776.7 link	c.203-1093A>G	intron_variant	Intron 2 of 10	1	NM_001609.4	ENSP00000357873.3
ACADSB	ENST00000368869.8 link	c.-4+2139A>G	intron_variant	Intron 2 of 9	2		ENSP00000357862.4
ACADSB	ENST00000411816.2 link	n.220-1093A>G	intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15715

AN:

152122

Hom.:

949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.103

AC:

15715

AN:

152240

Hom.:

948

Cov.:

AF XY:

0.107

AC XY:

7987

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0643

AC:

2669

AN:

41538

American (AMR)

AF:

0.0851

AC:

1302

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

237

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

722

AN:

5172

South Asian (SAS)

AF:

0.132

AC:

636

AN:

4828

European-Finnish (FIN)

AF:

0.204

AC:

2160

AN:

10598

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7630

AN:

68014

Other (OTH)

AF:

0.0843

AC:

178

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

721

1442

2163

2884

3605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0997

Hom.:

681

Bravo

AF:

0.0896

Asia WGS

AF:

0.137

AC:

478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.9

(source)

DANN

Benign

0.67

PhyloP100

0.23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over