12-120730280-T-C

Variant names:

• chr12-120730280-T-C
• rs3794215
• NM_000017.4:c.210+3091T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000017.4(ACADS):​c.210+3091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,080 control chromosomes in the GnomAD database, including 21,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21147 hom., cov: 32)
• Consequence: ACADS NM_000017.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADS	NM_000017.4	c.210+3091T>C		intron_variant	Intron 2 of 9	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.210+3091T>C		intron_variant	Intron 2 of 9		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.210+3091T>C		intron_variant	Intron 2 of 9	1	NM_000017.4	ENSP00000242592.4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77447 AN: 151960 Hom.: 21117 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77527 AN: 152080 Hom.: 21147 Cov.: 32 AF XY: 0.515 AC XY: 38288 AN XY: 74344

African (AFR) AF: 0.715 AC: 29668 AN: 41474

American (AMR) AF: 0.495 AC: 7574 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2547 AN: 5172

South Asian (SAS) AF: 0.566 AC: 2735 AN: 4830

European-Finnish (FIN) AF: 0.400 AC: 4225 AN: 10560

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27613 AN: 67974

Other (OTH) AF: 0.508 AC: 1073 AN: 2114

Alfa AF: 0.458 Hom.: 6374

Bravo AF: 0.526

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.38
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3794215; hg19: chr12-121168083;