1-75724646-C-G

Position:

• chr1-75724646-C-G

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.-142C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 876,744 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (188 hom., cov: 32)
  • Exomes 𝑓: 0.025 (291 hom.)
• Consequence: ACADM ENST00000541113.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.14

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=-0.87).
• BP6: Variant 1-75724646-C-G is Benign according to our data. Variant chr1-75724646-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 298065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.084 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.-142C>G		5_prime_UTR_variant	1/11	1
ACADM	ENST00000680805.1	c.-142C>G		5_prime_UTR_variant	1/11
ACADM	ENST00000680964.1	c.-142C>G		5_prime_UTR_variant	1/12

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6487 AN: 152158 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0253 AC: 18299 AN: 724470 Hom.: 291 Cov.: 10 AF XY: 0.0245 AC XY: 8996 AN XY: 367104

Gnomad4 AFR exome AF: 0.0831

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.00397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00750

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0426 AC: 6491 AN: 152274 Hom.: 188 Cov.: 32 AF XY: 0.0413 AC XY: 3076 AN XY: 74476

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0374 Hom.: 18

Bravo AF: 0.0454

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	- -

Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.61

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: rs61124994; hg19: chr1-76190331;