rs558314

Positions:

• chr12-120734000-C-G
• chr12-120734000-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACADS	NM_000017.4	c.211-2986C>G		intron_variant		ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.211-2986C>G		intron_variant			NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.211-2986C>G		intron_variant		1	NM_000017.4	ENSP00000242592	P1
ACADS	ENST00000411593.2	c.211-2986C>G		intron_variant		2		ENSP00000401045
ACADS	ENST00000539690.1	n.323-2986C>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.678

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs558314; hg19: chr12-121171803;