Variant 12-120725830-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000017.4(ACADS):c.-56C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000716 in 1,518,430 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00073 ( 11 hom. )

Consequence

ACADS
NM_000017.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.822

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADS	NM_000017.4 linkuse as main transcript	c.-56C>G		5_prime_UTR_variant	1/10	ENST00000242592.9
ACADS	NM_001302554.2 linkuse as main transcript	c.-56C>G		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ACADS	ENST00000242592.9 linkuse as main transcript	c.-56C>G	5_prime_UTR_variant	1/10	1	NM_000017.4	P1
ACADS	ENST00000539690.1 linkuse as main transcript	n.57C>G	non_coding_transcript_exon_variant	1/3	2
ACADS	ENST00000411593.2 linkuse as main transcript		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000735

AC:

1004

AN:

1366236

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

636

AN XY:

674964

show subpopulations

Gnomad4 AFR exome

AF:

0.000174

Gnomad4 AMR exome

AF:

0.000658

Gnomad4 ASJ exome

AF:

0.00110

Gnomad4 EAS exome

AF:

0.000500

Gnomad4 SAS exome

AF:

0.00756

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000545

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000530

Hom.:

Bravo

AF:

0.000397

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of butyryl-CoA dehydrogenase

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over