chr12-120739975-A-G

Position:

• chr12-120739975-A-G

Variant summary

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

The NM_000017.4(ACADS):​c.*527A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 168,110 control chromosomes in the GnomAD database, including 8,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7445 hom., cov: 32)
  • Exomes 𝑓: 0.31 (957 hom.)
• Consequence: ACADS NM_000017.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.391

Genes affected

ACADS (HGNC:90): (acyl-CoA dehydrogenase short chain) This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-120739975-A-G is Benign according to our data. Variant chr12-120739975-A-G is described in ClinVar as [Benign]. Clinvar id is 307453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADS	NM_000017.4	c.*527A>G		3_prime_UTR_variant	10/10	ENST00000242592.9
ACADS	NM_001302554.2	c.*527A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADS	ENST00000242592.9	c.*527A>G		3_prime_UTR_variant	10/10	1	NM_000017.4	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45303 AN: 151810 Hom.: 7444 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.314 AC: 5081 AN: 16182 Hom.: 957 Cov.: 0 AF XY: 0.319 AC XY: 2657 AN XY: 8340

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.0857

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.298 AC: 45324 AN: 151928 Hom.: 7445 Cov.: 32 AF XY: 0.304 AC XY: 22600 AN XY: 74254

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.339

Alfa AF: 0.340 Hom.: 11482

Bravo AF: 0.298

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9204; hg19: chr12-121177778;