NM_001609.4:c.203-1093A>G

Variant names:

• chr10-123036654-A-G
• rs17104498
• NM_001609.4:c.203-1093A>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 3 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	NM_001609.4	MANE Select	c.203-1093A>G		intron	N/A	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-4+2139A>G		intron	N/A	NP_001317103.1	P45954-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	ENST00000358776.7	TSL:1 MANE Select	c.203-1093A>G		intron	N/A	ENSP00000357873.3	P45954-1
	ACADSB	ENST00000908753.1		c.203-1093A>G		intron	N/A	ENSP00000578812.1
	ACADSB	ENST00000908750.1		c.203-1093A>G		intron	N/A	ENSP00000578809.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15715 AN: 152122 Hom.: 949 Cov.: 33

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.: 33 AF XY: 0.107 AC XY: 7987 AN XY: 74424

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: 10 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7630 AN: 68014

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		0.23
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: rs17104498; hg19: chr10-124796170;