rs12263012

Positions:

chr10-123009067-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001609.4(ACADSB):c.38G>A(p.Arg13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,546,378 control chromosomes in the GnomAD database, including 106,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7982 hom., cov: 32)

Exomes 𝑓: 0.37 ( 98339 hom. )

Consequence

ACADSB
NM_001609.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0260

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.1785836E-4).

BP6

Variant 10-123009067-G-A is Benign according to our data. Variant chr10-123009067-G-A is described in ClinVar as [Benign]. Clinvar id is 299068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADSB	NM_001609.4 linkuse as main transcript	c.38G>A	p.Arg13Lys	missense_variant	1/11	ENST00000358776.7	NP_001600.1
ACADSB	NM_001330174.3 linkuse as main transcript	c.-168G>A		5_prime_UTR_variant	1/10		NP_001317103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADSB	ENST00000358776.7 linkuse as main transcript	c.38G>A	p.Arg13Lys	missense_variant	1/11	1	NM_001609.4	ENSP00000357873	P1	P45954-1
ACADSB	ENST00000368869.8 linkuse as main transcript	c.-164G>A		splice_region_variant, 5_prime_UTR_variant	1/10	2		ENSP00000357862		P45954-2

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45237

AN:

151960

Hom.:

7985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.310

AC:

45435

AN:

146504

Hom.:

7805

AF XY:

0.311

AC XY:

24198

AN XY:

77696

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.369

AC:

513968

AN:

1394300

Hom.:

98339

Cov.:

AF XY:

0.365

AC XY:

251287

AN XY:

687992

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.297

AC:

45241

AN:

152078

Hom.:

7982

Cov.:

AF XY:

0.297

AC XY:

22051

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.371

Hom.:

16642

Bravo

AF:

0.276

TwinsUK

AF:

0.399

AC:

1481

ALSPAC

AF:

0.399

AC:

1537

ESP6500AA

AF:

0.118

AC:

388

ESP6500EA

AF:

0.362

AC:

2125

ExAC

AF:

0.261

AC:

6206

Asia WGS

AF:

0.173

AC:

604

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of 2-methylbutyryl-CoA dehydrogenase

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 17143180) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.084

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.32

MetaRNN

Benign

0.00042

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.060

REVEL

Benign

0.17

Sift

Benign

0.73

Sift4G

Benign

0.51

Polyphen

0.012

Vest4

0.048

MPC

0.058

ClinPred

0.0014

GERP RS

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over