rs632650

Positions:

• chr12-111693894-G-T

Variant summary

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

The NM_025247.6(ACAD10):​c.187+998G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,124 control chromosomes in the GnomAD database, including 2,235 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 0.17 (2235 hom., cov: 32)
• Consequence: ACAD10 NM_025247.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAD10	NM_025247.6	c.187+998G>T		intron_variant		ENST00000313698.9
ACAD10	NM_001136538.2	c.187+998G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD10	ENST00000313698.9	c.187+998G>T		intron_variant		1	NM_025247.6	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25434 AN: 152006 Hom.: 2239 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.167 AC: 25430 AN: 152124 Hom.: 2235 Cov.: 32 AF XY: 0.167 AC XY: 12445 AN XY: 74362

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.181

Alfa AF: 0.157 Hom.: 2784

Bravo AF: 0.171

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72

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: rs632650; hg19: chr12-112131698;