rs11592612

Variant names:

• chr10-123011339-C-G
• rs11592612
• NM_001609.4:c.42+2268C>G

Variant summary

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

The NM_001609.4(ACADSB):​c.42+2268C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,948 control chromosomes in the GnomAD database, including 7,771 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 0.29 (7771 hom., cov: 31)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADSB	NM_001609.4	c.42+2268C>G		intron_variant	Intron 1 of 10	ENST00000358776.7	NP_001600.1
ACADSB	NM_001330174.3	c.-164+2268C>G		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.42+2268C>G		intron_variant	Intron 1 of 10	1	NM_001609.4	ENSP00000357873.3
ACADSB	ENST00000368869.8	c.-164+2272C>G		intron_variant	Intron 1 of 9	2		ENSP00000357862.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43707 AN: 151830 Hom.: 7774 Cov.: 31

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.288 AC: 43707 AN: 151948 Hom.: 7771 Cov.: 31 AF XY: 0.287 AC XY: 21326 AN XY: 74270

African (AFR) AF: 0.0929 AC: 3851 AN: 41464

American (AMR) AF: 0.282 AC: 4308 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3470

East Asian (EAS) AF: 0.124 AC: 643 AN: 5168

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4863 AN: 10528

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26636 AN: 67922

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.331 Hom.: 1152

Bravo AF: 0.265

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.72
PhyloP100		-0.16
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: rs11592612; hg19: chr10-124770855;