rs11592612

Positions:

• chr10-123011339-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACADSB	NM_001609.4	c.42+2268C>G		intron_variant		ENST00000358776.7	NP_001600.1
ACADSB	NM_001330174.3	c.-164+2268C>G		intron_variant			NP_001317103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADSB	ENST00000358776.7	c.42+2268C>G		intron_variant		1	NM_001609.4	ENSP00000357873.3
ACADSB	ENST00000368869.8	c.-164+2272C>G		intron_variant		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

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.305

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

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

Other links and lift over

dbSNP: rs11592612; hg19: chr10-124770855;