rs12127402

chr1-75739958-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.227

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]

ACMG classification

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/exons	MANE	UniProt
ACADM	NM_000016.6	c.469-22C>A		intron_variant		ENST00000370841.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADM	ENST00000370841.9	c.469-22C>A		intron_variant		1	NM_000016.6	P4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37812 AN: 151968 Hom.: 5022 Cov.: 33

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

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.: 25 AF XY: 0.277 AC XY: 193381 AN XY: 699142

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.: 33 AF XY: 0.245 AC XY: 18241 AN XY: 74342

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:3

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	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -

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	-0.82
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

Other links and lift over

dbSNP: rs12127402; hg19: chr1-76205643;