10-123034081-A-G

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.43-275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,284 control chromosomes in the GnomAD database, including 1,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1392 hom., cov: 33)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.651

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=-0.86).
• BP6: Variant 10-123034081-A-G is Benign according to our data. Variant chr10-123034081-A-G is described in ClinVar as [Benign]. Clinvar id is 1180240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADSB	NM_001609.4	c.43-275A>G		intron_variant		ENST00000358776.7
ACADSB	NM_001330174.3	c.-163-275A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADSB	ENST00000358776.7	c.43-275A>G		intron_variant		1	NM_001609.4	P1
ACADSB	ENST00000368869.8	c.-163-275A>G		intron_variant		2
ACADSB	ENST00000411816.2	n.60-275A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19646 AN: 152166 Hom.: 1393 Cov.: 33

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.129 AC: 19647 AN: 152284 Hom.: 1392 Cov.: 33 AF XY: 0.126 AC XY: 9353 AN XY: 74470

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.150

Alfa AF: 0.160 Hom.: 2470

Bravo AF: 0.134

Asia WGS AF: 0.0490 AC: 171 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	-0.86
Cadd	Benign	7.0
Dann	Benign	0.75

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: rs4980245; hg19: chr10-124793597;