rs473041

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-134256718-T-C
• chr11-134256718-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014384.3(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 NM_014384.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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>C		intron	N/A	NP_055199.1	Q9UKU7-1
	ACAD8	NM_001441136.1		c.210+70T>C		intron	N/A	NP_001428065.1
	ACAD8	NM_001441138.1		c.86+70T>C		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>C		intron	N/A	ENSP00000281182.5	Q9UKU7-1
	ACAD8	ENST00000527082.5	TSL:1	n.234+70T>C		intron	N/A
	ACAD8	ENST00000531338.5	TSL:1	n.66+70T>C		intron	N/A

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

African (AFR) AF: 0.123 AC: 3353 AN: 27360

American (AMR) AF: 0.421 AC: 15987 AN: 37984

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 9941 AN: 22192

East Asian (EAS) AF: 0.237 AC: 9046 AN: 38156

South Asian (SAS) AF: 0.321 AC: 23732 AN: 73910

European-Finnish (FIN) AF: 0.216 AC: 10945 AN: 50632

Middle Eastern (MID) AF: 0.407 AC: 2073 AN: 5094

European-Non Finnish (NFE) AF: 0.332 AC: 289886 AN: 872956

Other (OTH) AF: 0.325 AC: 16450 AN: 50604

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

African (AFR) AF: 0.131 AC: 5433 AN: 41516

American (AMR) AF: 0.373 AC: 5694 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1190 AN: 5156

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2325 AN: 10608

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22529 AN: 67992

Other (OTH) AF: 0.312 AC: 657 AN: 2106

Alfa AF: 0.297 Hom.: 4434

Bravo AF: 0.280

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.35
PhyloP100		-0.16
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs473041;

hg19: chr11-134126612;

COSMIC: COSV55539557;

COSMIC: COSV55539557;