10-123025302-G-C

Variant names:

• chr10-123025302-G-C
• rs11248366
• NM_001609.4:c.43-9054G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001609.4(ACADSB):​c.43-9054G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,158 control chromosomes in the GnomAD database, including 18,977 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 0.48 (18977 hom., cov: 29)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADSB	NM_001609.4	c.43-9054G>C		intron_variant	Intron 1 of 10	ENST00000358776.7	NP_001600.1
ACADSB	NM_001330174.3	c.-163-9054G>C		intron_variant	Intron 1 of 9		NP_001317103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADSB	ENST00000358776.7	c.43-9054G>C		intron_variant	Intron 1 of 10	1	NM_001609.4	ENSP00000357873.3
ACADSB	ENST00000368869.8	c.-163-9054G>C		intron_variant	Intron 1 of 9	2		ENSP00000357862.4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73066 AN: 151040 Hom.: 18978 Cov.: 29

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.484 AC: 73092 AN: 151158 Hom.: 18977 Cov.: 29 AF XY: 0.477 AC XY: 35190 AN XY: 73806

African (AFR) AF: 0.343 AC: 14098 AN: 41128

American (AMR) AF: 0.461 AC: 6998 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2085 AN: 3464

East Asian (EAS) AF: 0.139 AC: 704 AN: 5062

South Asian (SAS) AF: 0.321 AC: 1531 AN: 4768

European-Finnish (FIN) AF: 0.551 AC: 5757 AN: 10450

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40154 AN: 67822

Other (OTH) AF: 0.519 AC: 1090 AN: 2100

Alfa AF: 0.518 Hom.: 2511

Bravo AF: 0.470

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.24
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11248366; hg19: chr10-124784818;