rs6490294

chr12-111752634-C-Achr12-111752634-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025247.6(ACAD10):c.2818-1138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,578 control chromosomes in the GnomAD database, including 13,965 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 0.35 (13965 hom., cov: 30)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: ACAD10 NM_025247.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

Genes affected

ACAD10 (HGNC:21597): (acyl-CoA dehydrogenase family member 10) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes (ACADs), which participate in the beta-oxidation of fatty acids in mitochondria. The encoded enzyme contains a hydrolase domain at the N-terminal portion, a serine/threonine protein kinase catlytic domain in the central region, and a conserved ACAD domain at the C-terminus. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAD10	NM_025247.6	c.2818-1138C>A		intron_variant		ENST00000313698.9
ACAD10	NM_001136538.2	c.2911-1138C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD10	ENST00000313698.9	c.2818-1138C>A		intron_variant		1	NM_025247.6	P1
ACAD10	ENST00000455480.6	c.2911-1138C>A		intron_variant		1
ACAD10	ENST00000508303.5	n.1888-3034C>A		intron_variant, non_coding_transcript_variant		2
ACAD10	ENST00000547491.1	n.601-1138C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53645 AN: 151446 Hom.: 13925 Cov.: 30

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

GnomAD4 genome AF: 0.355 AC: 53746 AN: 151562 Hom.: 13965 Cov.: 30 AF XY: 0.354 AC XY: 26255 AN XY: 74074

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.333

Alfa AF: 0.216 Hom.: 5114

Bravo AF: 0.388

Asia WGS AF: 0.531 AC: 1845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.47

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: rs6490294; hg19: chr12-112190438;