chr11-134256718-T-C

Position:

• chr11-134256718-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000281182.9(ACAD8):​c.210+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,331,044 control chromosomes in the GnomAD database, including 70,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6183 hom., cov: 32)
  • Exomes 𝑓: 0.32 (64153 hom.)
• Consequence: ACAD8 ENST00000281182.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.158

Genes affected

ACAD8 (HGNC:87): (acyl-CoA dehydrogenase family member 8) This gene encodes 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. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-134256718-T-C is Benign according to our data. Variant chr11-134256718-T-C is described in ClinVar as [Benign]. Clinvar id is 1223942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAD8	NM_014384.3	c.210+70T>C		intron_variant		ENST00000281182.9	NP_055199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAD8	ENST00000281182.9	c.210+70T>C		intron_variant		1	NM_014384.3	ENSP00000281182	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41204 AN: 152038 Hom.: 6181 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.324 AC: 381413 AN: 1178888 Hom.: 64153 Cov.: 15 AF XY: 0.325 AC XY: 193343 AN XY: 595328

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.271 AC: 41221 AN: 152156 Hom.: 6183 Cov.: 32 AF XY: 0.270 AC XY: 20055 AN XY: 74372

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.312

Alfa AF: 0.289 Hom.: 2548

Bravo AF: 0.280

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.35

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: rs473041; hg19: chr11-134126612; COSMIC: COSV55539557; COSMIC: COSV55539557;