chr12-120739469-G-C

Position:

• chr12-120739469-G-C

Variant summary

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

The ENST00000242592.9(ACADS):​c.*21G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,599,860 control chromosomes in the GnomAD database, including 54,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4370 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50453 hom.)
• Consequence: ACADS ENST00000242592.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.11

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=-0.83).
• BP6: Variant 12-120739469-G-C is Benign according to our data. Variant chr12-120739469-G-C is described in ClinVar as [Benign]. Clinvar id is 254692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADS	NM_000017.4	c.*21G>C		3_prime_UTR_variant	10/10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.*21G>C		3_prime_UTR_variant	10/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.*21G>C		3_prime_UTR_variant	10/10	1	NM_000017.4	ENSP00000242592	P1
ACADS	ENST00000411593.2	c.*21G>C		3_prime_UTR_variant	10/10	2		ENSP00000401045

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33368 AN: 152120 Hom.: 4364 Cov.: 33

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.270 AC: 61810 AN: 229280 Hom.: 8950 AF XY: 0.270 AC XY: 34310 AN XY: 126962

Gnomad AFR exome AF: 0.0840

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.300

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.260 AC: 376486 AN: 1447622 Hom.: 50453 Cov.: 35 AF XY: 0.262 AC XY: 188755 AN XY: 719628

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.219 AC: 33376 AN: 152238 Hom.: 4370 Cov.: 33 AF XY: 0.226 AC XY: 16849 AN XY: 74444

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.258

Alfa AF: 0.200 Hom.: 701

Bravo AF: 0.216

Asia WGS AF: 0.250 AC: 865 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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:2

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.67

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: rs3916; hg19: chr12-121177272; COSMIC: COSV54368611; COSMIC: COSV54368611;