rs3914

Variant names:

• chr12-120737096-T-C
• rs3914
• NM_000017.4:c.321T>C

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.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
• Publications: 33 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics, PanelApp Australia, Orphanet

ENSG00000255946 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 136259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.321T>C	p.Arg107Arg	synonymous	Exon 3 of 10	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.321T>C	p.Arg107Arg	synonymous	Exon 3 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.321T>C	p.Arg107Arg	synonymous	Exon 3 of 10	ENSP00000242592.4	P16219
	ACADS	ENST00000946559.1		c.321T>C	p.Arg107Arg	synonymous	Exon 3 of 10	ENSP00000616618.1
	ACADS	ENST00000893619.1		c.321T>C	p.Arg107Arg	synonymous	Exon 3 of 10	ENSP00000563678.1

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

GnomAD2 exomes AF: 0.521 AC: 113095 AN: 217102 AF XY: 0.521

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 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

African (AFR) AF: 0.639 AC: 21182 AN: 33148

American (AMR) AF: 0.614 AC: 25790 AN: 41988

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12366 AN: 25670

East Asian (EAS) AF: 0.485 AC: 18862 AN: 38920

South Asian (SAS) AF: 0.646 AC: 53746 AN: 83242

European-Finnish (FIN) AF: 0.455 AC: 23446 AN: 51486

Middle Eastern (MID) AF: 0.617 AC: 3545 AN: 5742

European-Non Finnish (NFE) AF: 0.441 AC: 485328 AN: 1101522

Other (OTH) AF: 0.496 AC: 29588 AN: 59606

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

African (AFR) AF: 0.631 AC: 26210 AN: 41550

American (AMR) AF: 0.568 AC: 8694 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1661 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2795 AN: 5164

South Asian (SAS) AF: 0.639 AC: 3086 AN: 4828

European-Finnish (FIN) AF: 0.461 AC: 4890 AN: 10598

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30323 AN: 67982

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.482 Hom.: 27681

Bravo AF: 0.531

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Deficiency of butyryl-CoA dehydrogenase (4)
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs3914; hg19: chr12-121174899; COSMIC: COSV54370098; COSMIC: COSV54370098;