rs7070793

Variant names:

• chr10-123029670-A-G
• rs7070793
• NM_001609.4:c.43-4686A>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.43-4686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,004 control chromosomes in the GnomAD database, including 19,757 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 0.49 (19757 hom., cov: 32)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 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.43-4686A>G		intron	N/A	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-163-4686A>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.43-4686A>G		intron	N/A	ENSP00000357873.3	P45954-1
	ACADSB	ENST00000908753.1		c.43-4686A>G		intron	N/A	ENSP00000578812.1
	ACADSB	ENST00000908750.1		c.43-4686A>G		intron	N/A	ENSP00000578809.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74806 AN: 151884 Hom.: 19757 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.492 AC: 74840 AN: 152004 Hom.: 19757 Cov.: 32 AF XY: 0.487 AC XY: 36209 AN XY: 74304

African (AFR) AF: 0.333 AC: 13814 AN: 41450

American (AMR) AF: 0.468 AC: 7146 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1300 AN: 5178

South Asian (SAS) AF: 0.336 AC: 1616 AN: 4814

European-Finnish (FIN) AF: 0.557 AC: 5866 AN: 10534

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41182 AN: 67976

Other (OTH) AF: 0.522 AC: 1102 AN: 2110

Alfa AF: 0.565 Hom.: 79437

Bravo AF: 0.480

Asia WGS AF: 0.302 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-1.4
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: rs7070793; hg19: chr10-124789186;