rs76543640

Positions:

chr12-120737135-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.360C>T(p.Asn120=) 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:6

Conservation

PhyloP100: -2.97

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=-0.8).

BP6

Variant 12-120737135-C-T is Benign according to our data. Variant chr12-120737135-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
ACADS	NM_000017.4 linkuse as main transcript	c.360C>T	p.Asn120=	splice_region_variant, synonymous_variant	3/10	ENST00000242592.9
ACADS	NM_001302554.2 linkuse as main transcript	c.360C>T	p.Asn120=	splice_region_variant, synonymous_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ACADS	ENST00000242592.9 linkuse as main transcript	c.360C>T	p.Asn120=	splice_region_variant, synonymous_variant	3/10	1	NM_000017.4	P1
ACADS	ENST00000411593.2 linkuse as main transcript	c.360C>T	p.Asn120=	splice_region_variant, synonymous_variant	3/10	2
ACADS	ENST00000539690.1 linkuse as main transcript	n.472C>T		non_coding_transcript_exon_variant	3/3	2

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

GnomAD3 exomes

AF:

0.0367

AC:

7034

AN:

191684

Hom.:

596

AF XY:

0.0382

AC XY:

3928

AN XY:

102828

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 SAS exome

AF:

0.0673

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

Gnomad4 AFR exome

AF:

0.00540

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00502

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.00940

Gnomad4 NFE exome

AF:

0.00666

Gnomad4 OTH exome

AF:

0.0301

GnomAD4 genome

AF:

0.0188

AC:

2871

AN:

152370

Hom.:

237

Cov.:

AF XY:

0.0213

AC XY:

1587

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00447

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.0770

Gnomad4 FIN

AF:

0.00743

Gnomad4 NFE

AF:

0.00855

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0168

Hom.:

182

Bravo

AF:

0.0186

Asia WGS

AF:

0.146

AC:

506

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2014	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, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 30, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Deficiency of butyryl-CoA dehydrogenase

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.021

DANN

Benign

0.90

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

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