chr1-75724531-G-A

Position:

• chr1-75724531-G-A

Variant summary

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

The ENST00000541113.6(ACADM):​c.-257G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 411,780 control chromosomes in the GnomAD database, including 16,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5739 hom., cov: 31)
  • Exomes 𝑓: 0.28 (10987 hom.)
• Consequence: ACADM ENST00000541113.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.23

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=-0.88).
• BP6: Variant 1-75724531-G-A is Benign according to our data. Variant chr1-75724531-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 298063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADM	ENST00000541113.6	c.-257G>A		5_prime_UTR_variant	1/11	1
ACADM	ENST00000680805.1	c.-257G>A		5_prime_UTR_variant	1/11
ACADM	ENST00000680964.1	c.-257G>A		5_prime_UTR_variant	1/12

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40880 AN: 151966 Hom.: 5738 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.276 AC: 71619 AN: 259696 Hom.: 10987 Cov.: 2 AF XY: 0.276 AC XY: 37174 AN XY: 134446

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.269 AC: 40878 AN: 152084 Hom.: 5739 Cov.: 31 AF XY: 0.268 AC XY: 19924 AN XY: 74310

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.293

Alfa AF: 0.154 Hom.: 310

Bravo AF: 0.264

Asia WGS AF: 0.131 AC: 456 AN: 3476

ClinVar

Significance: Benign/Likely 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, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.88
CADD	Benign	0.78
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs17848068; hg19: chr1-76190216;