rs3915

Variant names:

• chr12-120738876-C-T
• rs3915
• NM_000017.4:c.990C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-120738876-C-T
• chr12-120738876-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000017.4(ACADS):​c.990C>T​(p.Arg330Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,613,652 control chromosomes in the GnomAD database, including 200,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (29570 hom., cov: 34)
  • Exomes 𝑓: 0.47 (170549 hom.)
• Consequence: ACADS NM_000017.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.49
• Publications: 34 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 12-120738876-C-T is Benign according to our data. Variant chr12-120738876-C-T is described in ClinVar as Benign. ClinVar VariationId is 136260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 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.990C>T	p.Arg330Arg	synonymous	Exon 8 of 10	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.978C>T	p.Arg326Arg	synonymous	Exon 8 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.990C>T	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000242592.4	P16219
	ACADS	ENST00000946559.1		c.990C>T	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000616618.1
	ACADS	ENST00000893619.1		c.990C>T	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000563678.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90092 AN: 152058 Hom.: 29510 Cov.: 34

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.582

GnomAD2 exomes AF: 0.540 AC: 135420 AN: 250796 AF XY: 0.534

Gnomad AFR exome AF: 0.898

Gnomad AMR exome AF: 0.637

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.537

Gnomad FIN exome AF: 0.458

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.474 AC: 692370 AN: 1461476 Hom.: 170549 Cov.: 70 AF XY: 0.478 AC XY: 347486 AN XY: 727056

African (AFR) AF: 0.905 AC: 30290 AN: 33480

American (AMR) AF: 0.630 AC: 28180 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 12642 AN: 26136

East Asian (EAS) AF: 0.486 AC: 19302 AN: 39700

South Asian (SAS) AF: 0.646 AC: 55755 AN: 86250

European-Finnish (FIN) AF: 0.451 AC: 23913 AN: 53054

Middle Eastern (MID) AF: 0.631 AC: 3637 AN: 5766

European-Non Finnish (NFE) AF: 0.439 AC: 487861 AN: 1111980

Other (OTH) AF: 0.510 AC: 30790 AN: 60388

GnomAD4 genome AF: 0.593 AC: 90205 AN: 152176 Hom.: 29570 Cov.: 34 AF XY: 0.598 AC XY: 44475 AN XY: 74370

African (AFR) AF: 0.887 AC: 36838 AN: 41554

American (AMR) AF: 0.591 AC: 9042 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1664 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2787 AN: 5154

South Asian (SAS) AF: 0.639 AC: 3082 AN: 4822

European-Finnish (FIN) AF: 0.457 AC: 4841 AN: 10592

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30139 AN: 67964

Other (OTH) AF: 0.585 AC: 1236 AN: 2114

Alfa AF: 0.509 Hom.: 19178

Bravo AF: 0.614

Asia WGS AF: 0.635 AC: 2205 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Deficiency of butyryl-CoA dehydrogenase (4)
-	-	4	not specified (4)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.023
DANN	Benign	0.85
PhyloP100		-1.5
Mutation Taster		=100/0	disease causing (ClinVar)

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: rs3915; hg19: chr12-121176679; COSMIC: COSV54369740; COSMIC: COSV54369740;