10-123009383-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADSB	NM_001609.4	c.42+312G>C		intron_variant		ENST00000358776.7
ACADSB	NM_001330174.3	c.-164+312G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADSB	ENST00000358776.7	c.42+312G>C		intron_variant		1	NM_001609.4	P1
ACADSB	ENST00000368869.8	c.-164+316G>C		intron_variant		2

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

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.144

Alfa AF: 0.159 Hom.: 251

Bravo AF: 0.132

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.7
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs12220683; hg19: chr10-124768899;