rs7070793

Positions:

• chr10-123029670-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADSB	NM_001609.4	c.43-4686A>G		intron_variant		ENST00000358776.7
ACADSB	NM_001330174.3	c.-163-4686A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADSB	ENST00000358776.7	c.43-4686A>G		intron_variant		1	NM_001609.4	P1
ACADSB	ENST00000368869.8	c.-163-4686A>G		intron_variant		2
ACADSB	ENST00000411816.2	n.59+2078A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.522

Alfa AF: 0.582 Hom.: 53074

Bravo AF: 0.480

Asia WGS AF: 0.302 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.51

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: rs7070793; hg19: chr10-124789186;