rs3916

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:5

Conservation

PhyloP100: -1.11

Publications

45 publications found

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 Gene-Disease associations (from GenCC):

short chain acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, ClinGen

ACADS links:

ENSG00000255946 (HGNC:):

ENSG00000255946 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ACADS	NM_000017.4 link	c.*21G>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000242592.9	NP_000008.1	P16219E5KSD5
ACADS	NM_001302554.2 link	c.*21G>C		3_prime_UTR_variant	Exon 10 of 10		NP_001289483.1	P16219E9PE82B4DUH1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACADS	ENST00000242592.9 link	c.*21G>C	3_prime_UTR_variant	Exon 10 of 10	1	NM_000017.4	ENSP00000242592.4	P16219
ACADS	ENST00000411593.2 link	c.*21G>C	3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000401045.2	E9PE82
ENSG00000255946	ENST00000724268.1 link	n.305-9181C>G	intron_variant	Intron 1 of 1

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

GnomAD2 exomes

AF:

0.270

AC:

61810

AN:

229280

AF XY:

0.270

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 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

African (AFR)

AF:

0.0837

AC:

2789

AN:

33328

American (AMR)

AF:

0.363

AC:

16077

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

8801

AN:

26022

East Asian (EAS)

AF:

0.142

AC:

5612

AN:

39488

South Asian (SAS)

AF:

0.298

AC:

25661

AN:

85980

European-Finnish (FIN)

AF:

0.264

AC:

11911

AN:

45178

Middle Eastern (MID)

AF:

0.365

AC:

1676

AN:

4596

European-Non Finnish (NFE)

AF:

0.260

AC:

287931

AN:

1108804

Other (OTH)

AF:

0.268

AC:

16028

AN:

59894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

15531

31061

46592

62122

77653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9632

19264

28896

38528

48160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33376

AN:

152238

Hom.:

4370

Cov.:

AF XY:

0.226

AC XY:

16849

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0903

AC:

3750

AN:

41532

American (AMR)

AF:

0.315

AC:

4821

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1148

AN:

3468

East Asian (EAS)

AF:

0.144

AC:

746

AN:

5180

South Asian (SAS)

AF:

0.282

AC:

1362

AN:

4832

European-Finnish (FIN)

AF:

0.270

AC:

2864

AN:

10610

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17777

AN:

67994

Other (OTH)

AF:

0.258

AC:

545

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1335

2670

4004

5339

6674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.77

(source)

DANN

Benign

0.67

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over