Variant 12-120738181-T-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.625-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,590,938 control chromosomes in the GnomAD database, including 180,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21279 hom., cov: 32)

Exomes 𝑓: 0.47 ( 159352 hom. )

Consequence

ACADS
NM_000017.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.065955E-6).

BP6

Variant 12-120738181-T-C is Benign according to our data. Variant chr12-120738181-T-C is described in ClinVar as [Benign]. Clinvar id is 1188992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120738181-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADS	NM_000017.4 linkuse as main transcript	c.625-99T>C		intron_variant		ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2 linkuse as main transcript	c.605T>C	p.Leu202Pro	missense_variant	5/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9 linkuse as main transcript	c.625-99T>C		intron_variant		1	NM_000017.4	ENSP00000242592	P1
ACADS	ENST00000411593.2 linkuse as main transcript	c.605T>C	p.Leu202Pro	missense_variant	5/10	2		ENSP00000401045

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79102

AN:

151788

Hom.:

21249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.520

AC:

109704

AN:

210954

Hom.:

29142

AF XY:

0.520

AC XY:

59721

AN XY:

114818

show subpopulations

Gnomad AFR exome

AF:

0.647

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.537

Gnomad SAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.466

AC:

670092

AN:

1439032

Hom.:

159352

Cov.:

AF XY:

0.471

AC XY:

336306

AN XY:

714224

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.485

Gnomad4 SAS exome

AF:

0.645

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.438

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.521

AC:

79174

AN:

151906

Hom.:

21279

Cov.:

AF XY:

0.529

AC XY:

39258

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.478

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.485

Hom.:

3946

Bravo

AF:

0.531

TwinsUK

AF:

0.441

AC:

1637

ALSPAC

AF:

0.440

AC:

1694

ExAC

AF:

0.492

AC:

58933

Asia WGS

AF:

0.620

AC:

2155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Deficiency of butyryl-CoA dehydrogenase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.21

DANN

Benign

0.63

DEOGEN2

Benign

0.22

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000041

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

0.64

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.027

ClinPred

0.0046

GERP RS

-0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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