chr12-120737135-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000017.4(ACADS):c.360C>T(p.Asn120Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,579,494 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 237 hom., cov: 33)

Exomes 𝑓: 0.017 ( 1419 hom. )

Consequence

ACADS
NM_000017.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001347

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.97

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-120737135-C-T is Benign according to our data. Variant chr12-120737135-C-T is described in ClinVar as Benign. ClinVar VariationId is 196197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADS	NM_000017.4 link	c.360C>T	p.Asn120Asn	splice_region_variant, synonymous_variant	Exon 3 of 10	ENST00000242592.9	NP_000008.1	P16219E5KSD5
ACADS	NM_001302554.2 link	c.360C>T	p.Asn120Asn	splice_region_variant, synonymous_variant	Exon 3 of 10		NP_001289483.1	P16219E9PE82B4DUH1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACADS	ENST00000242592.9 link	c.360C>T	p.Asn120Asn	splice_region_variant, synonymous_variant	Exon 3 of 10	1	NM_000017.4	ENSP00000242592.4	P16219
ACADS	ENST00000411593.2 link	c.360C>T	p.Asn120Asn	splice_region_variant, synonymous_variant	Exon 3 of 10	2		ENSP00000401045.2	E9PE82
ACADS	ENST00000539690.1 link	n.472C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
ENSG00000255946	ENST00000724268.1 link	n.305-6847G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2862

AN:

152250

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00427

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.0765

Gnomad FIN

AF:

0.00743

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.0367

AC:

7034

AN:

191684

AF XY:

0.0382

show subpopulations

Gnomad AFR exome

AF:

0.00411

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.00534

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.00885

Gnomad NFE exome

AF:

0.00908

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0174

AC:

24770

AN:

1427124

Hom.:

1419

Cov.:

AF XY:

0.0188

AC XY:

13282

AN XY:

706738

show subpopulations

African (AFR)

AF:

0.00540

AC:

177

AN:

32794

American (AMR)

AF:

0.0132

AC:

528

AN:

40146

Ashkenazi Jewish (ASJ)

AF:

0.00502

AC:

128

AN:

25502

East Asian (EAS)

AF:

0.232

AC:

8800

AN:

38000

South Asian (SAS)

AF:

0.0661

AC:

5416

AN:

81952

European-Finnish (FIN)

AF:

0.00940

AC:

475

AN:

50558

Middle Eastern (MID)

AF:

0.0341

AC:

195

AN:

5724

European-Non Finnish (NFE)

AF:

0.00666

AC:

7277

AN:

1093464

Other (OTH)

AF:

0.0301

AC:

1774

AN:

58984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1424

2848

4272

5696

7120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.0188

AC:

2871

AN:

152370

Hom.:

237

Cov.:

AF XY:

0.0213

AC XY:

1587

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00447

AC:

186

AN:

41604

American (AMR)

AF:

0.0121

AC:

185

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1385

AN:

5172

South Asian (SAS)

AF:

0.0770

AC:

372

AN:

4832

European-Finnish (FIN)

AF:

0.00743

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00855

AC:

582

AN:

68032

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

127

254

381

508

635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0186

Hom.:

295

Bravo

AF:

0.0186

Asia WGS

AF:

0.146

AC:

506

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Dec 30, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deficiency of butyryl-CoA dehydrogenase

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.021

(source)

DANN

Benign

0.90

PhyloP100

-3.0

Mutation Taster

=76/24

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.076

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