rs75424980

Variant names:

• chr10-123034198-C-CA
• rs75424980
• NM_001609.4:c.43-156dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001609.4(ACADSB):​c.43-156dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 1.0 (76196 hom., cov: 0)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.236
• Publications: 0 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: Orphanet, PanelApp Australia, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-123034198-C-CA is Benign according to our data. Variant chr10-123034198-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1258728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 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.43-156dupA		intron	N/A	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-163-156dupA		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.43-158_43-157insA		intron	N/A	ENSP00000357873.3	P45954-1
	ACADSB	ENST00000908753.1		c.43-158_43-157insA		intron	N/A	ENSP00000578812.1
	ACADSB	ENST00000908750.1		c.43-158_43-157insA		intron	N/A	ENSP00000578809.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152275 AN: 152276 Hom.: 76137 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

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

GnomAD4 genome AF: 1.00 AC: 152393 AN: 152394 Hom.: 76196 Cov.: 0 AF XY: 1.00 AC XY: 74515 AN XY: 74516

African (AFR) AF: 1.00 AC: 41592 AN: 41592

American (AMR) AF: 1.00 AC: 15310 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68049 AN: 68050

Other (OTH) AF: 1.00 AC: 2114 AN: 2114

Alfa AF: 1.00 Hom.: 8166

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
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: rs75424980; hg19: chr10-124793714;