12-120738876-C-T

Position:

chr12-120738876-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000017.4(ACADS):c.990C>T(p.Arg330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,613,652 control chromosomes in the GnomAD database, including 200,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29570 hom., cov: 34)

Exomes 𝑓: 0.47 ( 170549 hom. )

Consequence

ACADS
NM_000017.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.49

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 12-120738876-C-T is Benign according to our data. Variant chr12-120738876-C-T is described in ClinVar as [Benign]. Clinvar id is 136260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120738876-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 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.990C>T	p.Arg330=	synonymous_variant	8/10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2 linkuse as main transcript	c.978C>T	p.Arg326=	synonymous_variant	8/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9 linkuse as main transcript	c.990C>T	p.Arg330=	synonymous_variant	8/10	1	NM_000017.4	ENSP00000242592	P1
ACADS	ENST00000411593.2 linkuse as main transcript	c.978C>T	p.Arg326=	synonymous_variant	8/10	2		ENSP00000401045

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

90092

AN:

152058

Hom.:

29510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.582

GnomAD3 exomes

AF:

0.540

AC:

135420

AN:

250796

Hom.:

38627

AF XY:

0.534

AC XY:

72547

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.898

Gnomad AMR exome

AF:

0.637

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.537

Gnomad SAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.474

AC:

692370

AN:

1461476

Hom.:

170549

Cov.:

AF XY:

0.478

AC XY:

347486

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.905

Gnomad4 AMR exome

AF:

0.630

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.646

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.510

GnomAD4 genome

AF:

0.593

AC:

90205

AN:

152176

Hom.:

29570

Cov.:

AF XY:

0.598

AC XY:

44475

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.591

Gnomad4 ASJ

AF:

0.479

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.505

Hom.:

14483

Bravo

AF:

0.614

Asia WGS

AF:

0.635

AC:

2205

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2013	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Deficiency of butyryl-CoA dehydrogenase

Benign:4

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.023

DANN

Benign

0.85

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

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