1-75733660-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:5

Conservation

PhyloP100: -1.39

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

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

ACADM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000016.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACADM	NM_000016.6	MANE Select	c.387+32C>G	intron	N/A	NP_000007.1
ACADM	NM_001286043.2		c.486+32C>G	intron	N/A	NP_001272972.1
ACADM	NM_001127328.3		c.399+32C>G	intron	N/A	NP_001120800.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACADM	ENST00000370841.9	TSL:1 MANE Select	c.387+32C>G	intron	N/A	ENSP00000359878.5
ACADM	ENST00000370834.9	TSL:1	c.486+32C>G	intron	N/A	ENSP00000359871.5
ACADM	ENST00000420607.6	TSL:1	c.399+32C>G	intron	N/A	ENSP00000409612.2

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

GnomAD2 exomes

AF:

0.276

AC:

69231

AN:

251068

AF XY:

0.273

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 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

African (AFR)

AF:

0.293

AC:

9240

AN:

31494

American (AMR)

AF:

0.312

AC:

13911

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5508

AN:

25544

East Asian (EAS)

AF:

0.0304

AC:

1191

AN:

39214

South Asian (SAS)

AF:

0.197

AC:

16669

AN:

84430

European-Finnish (FIN)

AF:

0.282

AC:

15017

AN:

53338

Middle Eastern (MID)

AF:

0.256

AC:

1440

AN:

5636

European-Non Finnish (NFE)

AF:

0.334

AC:

343029

AN:

1028284

Other (OTH)

AF:

0.294

AC:

16840

AN:

57330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

13628

27257

40885

54514

68142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10576

21152

31728

42304

52880

<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:

0.299

AC:

45473

AN:

151852

Hom.:

6987

Cov.:

AF XY:

0.294

AC XY:

21837

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.287

AC:

11886

AN:

41368

American (AMR)

AF:

0.326

AC:

4983

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

744

AN:

3472

East Asian (EAS)

AF:

0.0348

AC:

180

AN:

5168

South Asian (SAS)

AF:

0.200

AC:

964

AN:

4808

European-Finnish (FIN)

AF:

0.285

AC:

3000

AN:

10510

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22722

AN:

67940

Other (OTH)

AF:

0.295

AC:

623

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1613

3226

4840

6453

8066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.297

Hom.:

1240

Bravo

AF:

0.302

Asia WGS

AF:

0.183

AC:

635

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Medium-chain acyl-coenzyme A dehydrogenase deficiency

Benign:2

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.072

(source)

DANN

Benign

0.63

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over