Genetic Variant NM_000017.4:c.473-116T>C (chr12-120737721-T-C) – ACMG Classification: Benign (-20 pts)

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.473-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,468,580 control chromosomes in the GnomAD database, including 49,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4334 hom., cov: 33)

Exomes 𝑓: 0.26 ( 45608 hom. )

Consequence

ACADS
NM_000017.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.966

Publications

55 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, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

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=-0.87).

BP6

Variant 12-120737721-T-C is Benign according to our data. Variant chr12-120737721-T-C is described in ClinVar as Benign. ClinVar VariationId is 676089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000017.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	NM_000017.4	MANE Select	c.473-116T>C		intron	N/A	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.472+254T>C		intron	N/A	NP_001289483.1	E9PE82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACADS	ENST00000242592.9	TSL:1 MANE Select	c.473-116T>C	intron	N/A	ENSP00000242592.4	P16219
ACADS	ENST00000946559.1		c.473-116T>C	intron	N/A	ENSP00000616618.1
ACADS	ENST00000893619.1		c.473-116T>C	intron	N/A	ENSP00000563678.1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33169

AN:

152016

Hom.:

4328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.259

AC:

340472

AN:

1316446

Hom.:

45608

Cov.:

AF XY:

0.260

AC XY:

170142

AN XY:

653314

show subpopulations

African (AFR)

AF:

0.0834

AC:

2561

AN:

30720

American (AMR)

AF:

0.362

AC:

13588

AN:

37524

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

7764

AN:

22840

East Asian (EAS)

AF:

0.119

AC:

4547

AN:

38080

South Asian (SAS)

AF:

0.293

AC:

22374

AN:

76260

European-Finnish (FIN)

AF:

0.266

AC:

11765

AN:

44214

Middle Eastern (MID)

AF:

0.363

AC:

1577

AN:

4346

European-Non Finnish (NFE)

AF:

0.260

AC:

261667

AN:

1007578

Other (OTH)

AF:

0.267

AC:

14629

AN:

54884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

13795

27591

41386

55182

68977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8662

17324

25986

34648

43310

<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:

0.218

AC:

33177

AN:

152134

Hom.:

4334

Cov.:

AF XY:

0.225

AC XY:

16728

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0898

AC:

3727

AN:

41524

American (AMR)

AF:

0.314

AC:

4809

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1149

AN:

3470

East Asian (EAS)

AF:

0.123

AC:

636

AN:

5164

South Asian (SAS)

AF:

0.277

AC:

1336

AN:

4822

European-Finnish (FIN)

AF:

0.270

AC:

2861

AN:

10592

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17752

AN:

67950

Other (OTH)

AF:

0.258

AC:

544

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1281

2561

3842

5122

6403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.247

Hom.:

15301

Bravo

AF:

0.215

Asia WGS

AF:

0.238

AC:

824

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.70

(source)

DANN

Benign

0.71

PhyloP100

-0.97

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over