NM_025247.6:c.187+8A>G

Variant names:

• chr12-111692904-A-G
• rs7132509
• NM_025247.6:c.187+8A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025247.6(ACAD10):​c.187+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,612,982 control chromosomes in the GnomAD database, including 11,792 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (1618 hom., cov: 32)
  • Exomes 𝑓: 0.036 (10174 hom.)
• Consequence: ACAD10 NM_025247.6 splice_region, intron
• Scores: Splicing: ADA: 0.00003145
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025247.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD10	NM_025247.6	MANE Select	c.187+8A>G		splice_region intron	N/A	NP_079523.3
	ACAD10	NM_001136538.2		c.187+8A>G		splice_region intron	N/A	NP_001130010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD10	ENST00000313698.9	TSL:1 MANE Select	c.187+8A>G		splice_region intron	N/A	ENSP00000325137.5
	ACAD10	ENST00000455480.6	TSL:1	c.187+8A>G		splice_region intron	N/A	ENSP00000389813.2
	ACAD10	ENST00000507135.5	TSL:1	n.359+8A>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11870 AN: 151946 Hom.: 1620 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.0824

GnomAD2 exomes AF: 0.0971 AC: 24184 AN: 249034 AF XY: 0.0873

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.00524

Gnomad EAS exome AF: 0.654

Gnomad FIN exome AF: 0.00368

Gnomad NFE exome AF: 0.00395

Gnomad OTH exome AF: 0.0560

GnomAD4 exome AF: 0.0357 AC: 52181 AN: 1460918 Hom.: 10174 Cov.: 31 AF XY: 0.0358 AC XY: 26026 AN XY: 726750

African (AFR) AF: 0.148 AC: 4964 AN: 33462

American (AMR) AF: 0.175 AC: 7816 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00526 AC: 137 AN: 26058

East Asian (EAS) AF: 0.645 AC: 25584 AN: 39682

South Asian (SAS) AF: 0.0798 AC: 6880 AN: 86178

European-Finnish (FIN) AF: 0.00334 AC: 178 AN: 53294

Middle Eastern (MID) AF: 0.0423 AC: 244 AN: 5762

European-Non Finnish (NFE) AF: 0.00262 AC: 2914 AN: 1111486

Other (OTH) AF: 0.0574 AC: 3464 AN: 60350

GnomAD4 genome AF: 0.0782 AC: 11892 AN: 152064 Hom.: 1618 Cov.: 32 AF XY: 0.0830 AC XY: 6170 AN XY: 74338

African (AFR) AF: 0.143 AC: 5945 AN: 41474

American (AMR) AF: 0.117 AC: 1786 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3193 AN: 5146

South Asian (SAS) AF: 0.102 AC: 494 AN: 4822

European-Finnish (FIN) AF: 0.00208 AC: 22 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00357 AC: 243 AN: 67978

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.0293 Hom.: 216

Bravo AF: 0.0950

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.57
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs7132509; hg19: chr12-112130708; COSMIC: COSV58157594; COSMIC: COSV58157594;