Variant chr12-120739469-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000017.4(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
NM_000017.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.11

Variant links:

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]

ACADS links:

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ACMG classification

Classification made for transcript

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	UniProt
ACADS	NM_000017.4 linkuse as main transcript	c.*21G>C		3_prime_UTR_variant	10/10	ENST00000242592.9
ACADS	NM_001302554.2 linkuse as main transcript	c.*21G>C		3_prime_UTR_variant	10/10

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33368

AN:

152120

Hom.:

4364

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.262

AC XY:

188755

AN XY:

719628

show subpopulations

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.:

AF XY:

0.226

AC XY:

16849

AN XY:

74444

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over