Genetic Variant NM_000017.4:c.360+21C>G (chr12-120737156-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000017.4(ACADS):c.360+21C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,565,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

ACADS
NM_000017.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0240

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-120737156-C-G is Benign according to our data. Variant chr12-120737156-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 254694.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADS	NM_000017.4 link	c.360+21C>G		intron_variant	Intron 3 of 9	ENST00000242592.9	NP_000008.1	P16219E5KSD5
ACADS	NM_001302554.2 link	c.360+21C>G		intron_variant	Intron 3 of 9		NP_001289483.1	P16219E9PE82B4DUH1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACADS	ENST00000242592.9 link	c.360+21C>G	intron_variant	Intron 3 of 9	1	NM_000017.4	ENSP00000242592.4	P16219
ACADS	ENST00000539690.1 link	n.493C>G	non_coding_transcript_exon_variant	Exon 3 of 3	2
ACADS	ENST00000411593.2 link	c.360+21C>G	intron_variant	Intron 3 of 9	2		ENSP00000401045.2	E9PE82
ENSG00000255946	ENST00000724268.1 link	n.305-6868G>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000580

AC:

AN:

172436

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000212

GnomAD4 exome

AF:

0.00000920

AC:

AN:

1413228

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

698694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32286

American (AMR)

AF:

0.00

AC:

AN:

37926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.00

AC:

AN:

36948

South Asian (SAS)

AF:

0.00

AC:

AN:

80782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

1086280

Other (OTH)

AF:

0.00

AC:

AN:

58462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000656

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely 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

0.83

(source)

DANN

Benign

0.71

PhyloP100

0.024

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over