17-7224575-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000018.4(ACADVL):c.1678+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,608,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 1 hom. )

Consequence

ACADVL
NM_000018.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:3

Conservation

PhyloP100: 0.716

Publications

0 publications found

Variant links:

Genes affected

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACADVL Gene-Disease associations (from GenCC):

very long chain acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACADVL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 17-7224575-C-T is Benign according to our data. Variant chr17-7224575-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 541727.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADVL	NM_000018.4 link	c.1678+23C>T		intron_variant	Intron 17 of 19	ENST00000356839.10	NP_000009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10 link	c.1678+23C>T		intron_variant	Intron 17 of 19	1	NM_000018.4	ENSP00000349297.5

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00160

AC:

389

AN:

243308

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00551

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00181

AC:

2640

AN:

1456148

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1277

AN XY:

724260

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33464

American (AMR)

AF:

0.000247

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.000290

AC:

AN:

86066

European-Finnish (FIN)

AF:

0.00487

AC:

238

AN:

48918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00201

AC:

2235

AN:

1111604

Other (OTH)

AF:

0.00199

AC:

120

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

169

338

508

677

846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152252

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41550

American (AMR)

AF:

0.000392

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00262

AC:

178

AN:

67994

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.00100

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Very long chain acyl-CoA dehydrogenase deficiency

Uncertain:4Benign:1

Oct 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2018

Counsyl

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Apr 05, 2018

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Nov 01, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The NM_000018.3:c.1678+23C>T (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7224575C>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant dose not meet any evidence codes reported in the ACMG guidelines. -

Jan 09, 2020

Natera, Inc.

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

ACADVL-related disorder

Benign:1

Jun 25, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Aug 27, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27246109) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.9

(source)

DANN

Benign

0.80

PhyloP100

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=21/79

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over