Variant rs2153126 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000016.6(ACADM):c.387+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,521,720 control chromosomes in the GnomAD database, including 75,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6987 hom., cov: 32)

Exomes 𝑓: 0.31 ( 68123 hom. )

Consequence

ACADM
NM_000016.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.39

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-75733660-C-G is Benign according to our data. Variant chr1-75733660-C-G is described in ClinVar as [Benign]. Clinvar id is 254689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADM	NM_000016.6 linkuse as main transcript	c.387+32C>G		intron_variant		ENST00000370841.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADM	ENST00000370841.9 linkuse as main transcript	c.387+32C>G		intron_variant		1	NM_000016.6	P4	P11310-1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45438

AN:

151734

Hom.:

6983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.0353

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.276

AC:

69231

AN:

251068

Hom.:

10188

AF XY:

0.273

AC XY:

37050

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.0261

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.309

AC:

422845

AN:

1369868

Hom.:

68123

Cov.:

AF XY:

0.304

AC XY:

209067

AN XY:

686918

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.0304

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.299

AC:

45473

AN:

151852

Hom.:

6987

Cov.:

AF XY:

0.294

AC XY:

21837

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.287

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.0348

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.297

Hom.:

1240

Bravo

AF:

0.302

Asia WGS

AF:

0.183

AC:

635

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.072

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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