rs2014355

chr12-120737721-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000017.4(ACADS):c.473-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,468,580 control chromosomes in the GnomAD database, including 49,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4334 hom., cov: 33)
  • Exomes 𝑓: 0.26 (45608 hom.)
• Consequence: ACADS NM_000017.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.966

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-120737721-T-C is Benign according to our data. Variant chr12-120737721-T-C is described in ClinVar as [Benign]. Clinvar id is 676089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADS	NM_000017.4	c.473-116T>C		intron_variant		ENST00000242592.9
ACADS	NM_001302554.2	c.472+254T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADS	ENST00000242592.9	c.473-116T>C		intron_variant		1	NM_000017.4	P1
ACADS	ENST00000411593.2	c.472+254T>C		intron_variant		2
ACADS	ENST00000539690.1	n.1058T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33169 AN: 152016 Hom.: 4328 Cov.: 33

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.259 AC: 340472 AN: 1316446 Hom.: 45608 Cov.: 20 AF XY: 0.260 AC XY: 170142 AN XY: 653314

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.218 AC: 33177 AN: 152134 Hom.: 4334 Cov.: 33 AF XY: 0.225 AC XY: 16728 AN XY: 74370

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.258

Alfa AF: 0.256 Hom.: 6391

Bravo AF: 0.215

Asia WGS AF: 0.238 AC: 824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.70
Dann	Benign	0.71

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: rs2014355; hg19: chr12-121175524; COSMIC: COSV54369369; COSMIC: COSV54369369;