11-134256718-T-G

Variant names:

• chr11-134256718-T-G
• rs473041
• NM_014384.3:c.210+70T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014384.3(ACAD8):​c.210+70T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000847 in 1,181,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ACAD8 NM_014384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 10 publications found

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]

ACAD8 Gene-Disease associations (from GenCC):

• isobutyryl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014384.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD8	NM_014384.3	MANE Select	c.210+70T>G		intron	N/A	NP_055199.1	Q9UKU7-1
	ACAD8	NM_001441136.1		c.210+70T>G		intron	N/A	NP_001428065.1
	ACAD8	NM_001441138.1		c.86+70T>G		intron	N/A	NP_001428067.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD8	ENST00000281182.9	TSL:1 MANE Select	c.210+70T>G		intron	N/A	ENSP00000281182.5	Q9UKU7-1
	ACAD8	ENST00000527082.5	TSL:1	n.234+70T>G		intron	N/A
	ACAD8	ENST00000531338.5	TSL:1	n.66+70T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.47e-7 AC: 1 AN: 1181248 Hom.: 0 Cov.: 15 AF XY: 0.00000168 AC XY: 1 AN XY: 596426

African (AFR) AF: 0.00 AC: 0 AN: 27376

American (AMR) AF: 0.00 AC: 0 AN: 38060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22230

East Asian (EAS) AF: 0.00 AC: 0 AN: 38168

South Asian (SAS) AF: 0.00 AC: 0 AN: 74010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5100

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 874986

Other (OTH) AF: 0.00 AC: 0 AN: 50650

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.44
PhyloP100		-0.16

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

Other links and lift over

dbSNP: rs473041; hg19: chr11-134126612;