10-123009383-G-C

Variant names:

• chr10-123009383-G-C
• rs12220683
• NM_001609.4:c.42+312G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001609.4(ACADSB):​c.42+312G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,144 control chromosomes in the GnomAD database, including 1,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1924 hom., cov: 32)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209
• 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: Orphanet, PanelApp Australia, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-123009383-G-C is Benign according to our data. Variant chr10-123009383-G-C is described in ClinVar as Benign. ClinVar VariationId is 1249547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 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.42+312G>C		intron	N/A	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-164+312G>C		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.42+312G>C		intron	N/A	ENSP00000357873.3	P45954-1
	ACADSB	ENST00000908753.1		c.42+312G>C		intron	N/A	ENSP00000578812.1
	ACADSB	ENST00000908750.1		c.42+312G>C		intron	N/A	ENSP00000578809.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21746 AN: 152026 Hom.: 1926 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.143 AC: 21752 AN: 152144 Hom.: 1924 Cov.: 32 AF XY: 0.147 AC XY: 10927 AN XY: 74370

African (AFR) AF: 0.0406 AC: 1685 AN: 41526

American (AMR) AF: 0.163 AC: 2487 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3470

East Asian (EAS) AF: 0.157 AC: 808 AN: 5160

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4808

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11970 AN: 67972

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.159 Hom.: 251

Bravo AF: 0.132

Asia WGS AF: 0.221 AC: 767 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
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.56
PhyloP100		-0.21
PromoterAI		-0.0075	Neutral
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: rs12220683; hg19: chr10-124768899;