12-120739469-G-C

Variant names:

• chr12-120739469-G-C
• rs3916
• NM_000017.4:c.*21G>C

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.*21G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,599,860 control chromosomes in the GnomAD database, including 54,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4370 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50453 hom.)
• Consequence: ACADS NM_000017.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.11
• Publications: 45 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, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000255946 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-120739469-G-C is Benign according to our data. Variant chr12-120739469-G-C is described in ClinVar as Benign. ClinVar VariationId is 254692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	NM_000017.4	MANE Select	c.*21G>C		3_prime_UTR	Exon 10 of 10	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.*21G>C		3_prime_UTR	Exon 10 of 10	NP_001289483.1	E9PE82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	ENST00000242592.9	TSL:1 MANE Select	c.*21G>C		3_prime_UTR	Exon 10 of 10	ENSP00000242592.4	P16219
	ACADS	ENST00000946559.1		c.*21G>C		3_prime_UTR	Exon 10 of 10	ENSP00000616618.1
	ACADS	ENST00000893619.1		c.*21G>C		3_prime_UTR	Exon 10 of 10	ENSP00000563678.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33368 AN: 152120 Hom.: 4364 Cov.: 33

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.270 AC: 61810 AN: 229280 AF XY: 0.270

Gnomad AFR exome AF: 0.0840

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.260 AC: 376486 AN: 1447622 Hom.: 50453 Cov.: 35 AF XY: 0.262 AC XY: 188755 AN XY: 719628

African (AFR) AF: 0.0837 AC: 2789 AN: 33328

American (AMR) AF: 0.363 AC: 16077 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8801 AN: 26022

East Asian (EAS) AF: 0.142 AC: 5612 AN: 39488

South Asian (SAS) AF: 0.298 AC: 25661 AN: 85980

European-Finnish (FIN) AF: 0.264 AC: 11911 AN: 45178

Middle Eastern (MID) AF: 0.365 AC: 1676 AN: 4596

European-Non Finnish (NFE) AF: 0.260 AC: 287931 AN: 1108804

Other (OTH) AF: 0.268 AC: 16028 AN: 59894

GnomAD4 genome AF: 0.219 AC: 33376 AN: 152238 Hom.: 4370 Cov.: 33 AF XY: 0.226 AC XY: 16849 AN XY: 74444

African (AFR) AF: 0.0903 AC: 3750 AN: 41532

American (AMR) AF: 0.315 AC: 4821 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.144 AC: 746 AN: 5180

South Asian (SAS) AF: 0.282 AC: 1362 AN: 4832

European-Finnish (FIN) AF: 0.270 AC: 2864 AN: 10610

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17777 AN: 67994

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.200 Hom.: 701

Bravo AF: 0.216

Asia WGS AF: 0.250 AC: 865 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Deficiency of butyryl-CoA dehydrogenase (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.67
PhyloP100		-1.1
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: rs3916; hg19: chr12-121177272; COSMIC: COSV54368611; COSMIC: COSV54368611;