chr12-120737096-T-C

Position:

• chr12-120737096-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000017.4(ACADS):​c.321T>C​(p.Arg107Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,593,530 control chromosomes in the GnomAD database, including 182,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21302 hom., cov: 35)
  • Exomes 𝑓: 0.47 (160839 hom.)
• Consequence: ACADS NM_000017.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.176

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-120737096-T-C is Benign according to our data. Variant chr12-120737096-T-C is described in ClinVar as [Benign]. Clinvar id is 136259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120737096-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.176 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADS	NM_000017.4	c.321T>C	p.Arg107Arg	synonymous_variant	3/10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.321T>C	p.Arg107Arg	synonymous_variant	3/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.321T>C	p.Arg107Arg	synonymous_variant	3/10	1	NM_000017.4	ENSP00000242592.4
ACADS	ENST00000411593.2	c.321T>C	p.Arg107Arg	synonymous_variant	3/10	2		ENSP00000401045.2
ACADS	ENST00000539690.1	n.433T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79289 AN: 152088 Hom.: 21272 Cov.: 35

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.532

GnomAD3 exomes AF: 0.521 AC: 113095 AN: 217102 Hom.: 30035 AF XY: 0.521 AC XY: 61011 AN XY: 117186

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.534

Gnomad SAS exome AF: 0.647

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.527

GnomAD4 exome AF: 0.468 AC: 673853 AN: 1441324 Hom.: 160839 Cov.: 67 AF XY: 0.473 AC XY: 337841 AN XY: 714954

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.521 AC: 79361 AN: 152206 Hom.: 21302 Cov.: 35 AF XY: 0.529 AC XY: 39353 AN XY: 74390

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.535

Alfa AF: 0.474 Hom.: 19768

Bravo AF: 0.531

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase Benign:4

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

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 29, 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, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.9
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs3914; hg19: chr12-121174899; COSMIC: COSV54370098; COSMIC: COSV54370098;