rs12570116

Variant names:

• chr10-123016959-C-T
• rs12570116
• NM_001609.4:c.42+7888C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001609.4(ACADSB):​c.42+7888C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 152,212 control chromosomes in the GnomAD database, including 12 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 0.0048 (12 hom., cov: 32)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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=-0.9).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00484 (736/152212) while in subpopulation AMR AF = 0.034 (520/15294). AF 95% confidence interval is 0.0316. There are 12 homozygotes in GnomAd4. There are 399 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	NM_001609.4	MANE Select	c.42+7888C>T		intron	N/A	NP_001600.1
	ACADSB	NM_001330174.3		c.-164+7888C>T		intron	N/A	NP_001317103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	ENST00000358776.7	TSL:1 MANE Select	c.42+7888C>T		intron	N/A	ENSP00000357873.3
	ACADSB	ENST00000368869.8	TSL:2	c.-164+7892C>T		intron	N/A	ENSP00000357862.4

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152094 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00575

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

GnomAD4 genome AF: 0.00484 AC: 736 AN: 152212 Hom.: 12 Cov.: 32 AF XY: 0.00536 AC XY: 399 AN XY: 74418

African (AFR) AF: 0.00125 AC: 52 AN: 41528

American (AMR) AF: 0.0340 AC: 520 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5164

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00364 Hom.: 2

Bravo AF: 0.00858

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs12570116; hg19: chr10-124776475;