11-134256374-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014384.3(ACAD8):​c.110-174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 152,280 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.037 ( 125 hom., cov: 33)

Consequence

ACAD8
NM_014384.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 11-134256374-A-G is Benign according to our data. Variant chr11-134256374-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 673123.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0372 (5670/152280) while in subpopulation AFR AF= 0.0437 (1815/41556). AF 95% confidence interval is 0.042. There are 125 homozygotes in gnomad4. There are 2715 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 125 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAD8NM_014384.3 linkuse as main transcriptc.110-174A>G intron_variant ENST00000281182.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAD8ENST00000281182.9 linkuse as main transcriptc.110-174A>G intron_variant 1 NM_014384.3 P1Q9UKU7-1

Frequencies

GnomAD3 genomes
AF:
0.0372
AC:
5666
AN:
152162
Hom.:
125
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0437
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.0227
Gnomad ASJ
AF:
0.0282
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00684
Gnomad FIN
AF:
0.0422
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0419
Gnomad OTH
AF:
0.0301
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0372
AC:
5670
AN:
152280
Hom.:
125
Cov.:
33
AF XY:
0.0365
AC XY:
2715
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0437
Gnomad4 AMR
AF:
0.0227
Gnomad4 ASJ
AF:
0.0282
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00705
Gnomad4 FIN
AF:
0.0422
Gnomad4 NFE
AF:
0.0419
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.0423
Hom.:
26
Bravo
AF:
0.0352
Asia WGS
AF:
0.0100
AC:
36
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
7.4
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35141157; hg19: chr11-134126268; API