Variant chr1-75728369-C-G 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.31-32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,560,352 control chromosomes in the GnomAD database, including 62,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4862 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57623 hom. )

Consequence

ACADM
NM_000016.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.313

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=-0.5).

BP6

Variant 1-75728369-C-G is Benign according to our data. Variant chr1-75728369-C-G is described in ClinVar as [Benign]. Clinvar id is 254691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 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.31-32C>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.31-32C>G		intron_variant		1	NM_000016.6	P4	P11310-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36816

AN:

151892

Hom.:

4863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.246

AC:

60819

AN:

246760

Hom.:

8046

AF XY:

0.246

AC XY:

32858

AN XY:

133486

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.0259

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.280

AC:

394000

AN:

1408342

Hom.:

57623

Cov.:

AF XY:

0.277

AC XY:

194568

AN XY:

703348

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.0303

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.242

AC:

36826

AN:

152010

Hom.:

4862

Cov.:

AF XY:

0.239

AC XY:

17775

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.0350

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.186

Hom.:

553

Bravo

AF:

0.239

Asia WGS

AF:

0.169

AC:

587

AN:

3474

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

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 08, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.3

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

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