dbSNP rs12127402: ACADM:c.469-22C>A (chr1-75739958-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000016.6(ACADM):c.469-22C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,560,800 control chromosomes in the GnomAD database, including 62,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5020 hom., cov: 33)

Exomes 𝑓: 0.28 ( 57511 hom. )

Consequence

ACADM
NM_000016.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.227

Variant links:

Genes affected

ACADM (HGNC:89): (acyl-CoA dehydrogenase medium chain) This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACADM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-75739958-C-A is Benign according to our data. Variant chr1-75739958-C-A is described in ClinVar as [Benign]. Clinvar id is 254690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADM	NM_000016.6 link	c.469-22C>A		intron_variant	Intron 6 of 11	ENST00000370841.9	NP_000007.1	P11310-1A0A0S2Z366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000370841.9 link	c.469-22C>A		intron_variant	Intron 6 of 11	1	NM_000016.6	ENSP00000359878.5		P11310-1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37812

AN:

151968

Hom.:

5022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.247

AC:

55471

AN:

224930

Hom.:

7248

AF XY:

0.246

AC XY:

30009

AN XY:

121796

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.0257

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.279

AC:

393519

AN:

1408716

Hom.:

57511

Cov.:

AF XY:

0.277

AC XY:

193381

AN XY:

699142

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.0301

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.249

AC:

37828

AN:

152084

Hom.:

5020

Cov.:

AF XY:

0.245

AC XY:

18241

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.0349

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.253

Alfa

AF:

0.261

Hom.:

969

Bravo

AF:

0.246

Asia WGS

AF:

0.170

AC:

589

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Benign:3

Mar 08, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 06, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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