rs9204

Variant names:

• chr12-120739975-A-G
• rs9204
• NM_000017.4:c.*527A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000017.4(ACADS):​c.*527A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 168,110 control chromosomes in the GnomAD database, including 8,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7445 hom., cov: 32)
  • Exomes 𝑓: 0.31 (957 hom.)
• Consequence: ACADS NM_000017.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.391
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• short chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, ClinGen

ENSG00000255946 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-120739975-A-G is Benign according to our data. Variant chr12-120739975-A-G is described in ClinVar as Benign. ClinVar VariationId is 307453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000017.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	NM_000017.4	MANE Select	c.*527A>G		3_prime_UTR	Exon 10 of 10	NP_000008.1
	ACADS	NM_001302554.2		c.*527A>G		3_prime_UTR	Exon 10 of 10	NP_001289483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	ENST00000242592.9	TSL:1 MANE Select	c.*527A>G		3_prime_UTR	Exon 10 of 10	ENSP00000242592.4
	ENSG00000255946	ENST00000542620.2	TSL:3	n.1134T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000255946	ENST00000724269.1		n.792T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45303 AN: 151810 Hom.: 7444 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.314 AC: 5081 AN: 16182 Hom.: 957 Cov.: 0 AF XY: 0.319 AC XY: 2657 AN XY: 8340

African (AFR) AF: 0.128 AC: 31 AN: 242

American (AMR) AF: 0.458 AC: 1092 AN: 2386

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 57 AN: 190

East Asian (EAS) AF: 0.0857 AC: 83 AN: 968

South Asian (SAS) AF: 0.338 AC: 571 AN: 1688

European-Finnish (FIN) AF: 0.315 AC: 151 AN: 480

Middle Eastern (MID) AF: 0.450 AC: 18 AN: 40

European-Non Finnish (NFE) AF: 0.300 AC: 2832 AN: 9430

Other (OTH) AF: 0.325 AC: 246 AN: 758

GnomAD4 genome AF: 0.298 AC: 45324 AN: 151928 Hom.: 7445 Cov.: 32 AF XY: 0.304 AC XY: 22600 AN XY: 74254

African (AFR) AF: 0.183 AC: 7601 AN: 41458

American (AMR) AF: 0.419 AC: 6397 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.124 AC: 641 AN: 5162

South Asian (SAS) AF: 0.369 AC: 1779 AN: 4818

European-Finnish (FIN) AF: 0.350 AC: 3693 AN: 10560

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22751 AN: 67882

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.328 Hom.: 29564

Bravo AF: 0.298

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of butyryl-CoA dehydrogenase (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9204; hg19: chr12-121177778;