12-120734000-C-G

Variant names:

• chr12-120734000-C-G
• rs558314
• NM_000017.4:c.211-2986C>G

Variant summary

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

The NM_000017.4(ACADS):​c.211-2986C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,030 control chromosomes in the GnomAD database, including 37,929 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 0.69 (37929 hom., cov: 31)
• Consequence: ACADS NM_000017.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADS	NM_000017.4	c.211-2986C>G		intron_variant	Intron 2 of 9	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.211-2986C>G		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.211-2986C>G		intron_variant	Intron 2 of 9	1	NM_000017.4	ENSP00000242592.4
ACADS	ENST00000411593.2	c.211-2986C>G		intron_variant	Intron 2 of 9	2		ENSP00000401045.2
ACADS	ENST00000539690.1	n.323-2986C>G		intron_variant	Intron 2 of 2	2
ENSG00000255946	ENST00000724268.1	n.305-3712G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104435 AN: 151912 Hom.: 37874 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.688 AC: 104545 AN: 152030 Hom.: 37929 Cov.: 31 AF XY: 0.694 AC XY: 51570 AN XY: 74294

African (AFR) AF: 0.921 AC: 38228 AN: 41496

American (AMR) AF: 0.719 AC: 10985 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2188 AN: 3460

East Asian (EAS) AF: 0.714 AC: 3685 AN: 5162

South Asian (SAS) AF: 0.764 AC: 3685 AN: 4822

European-Finnish (FIN) AF: 0.547 AC: 5779 AN: 10558

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37749 AN: 67952

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.435 Hom.: 975

Bravo AF: 0.708

Asia WGS AF: 0.747 AC: 2595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.77
PhyloP100		0.34
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: rs558314; hg19: chr12-121171803;