1-75724531-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.23
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]

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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=-0.88).
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
ACADMENST00000541113.6 linkuse as main transcriptc.-257G>A 5_prime_UTR_variant 1/111
ACADMENST00000680805.1 linkuse as main transcriptc.-257G>A 5_prime_UTR_variant 1/11
ACADMENST00000680964.1 linkuse as main transcriptc.-257G>A 5_prime_UTR_variant 1/12

Frequencies

GnomAD3 genomes
AF:
0.269
AC:
40880
AN:
151966
Hom.:
5738
Cov.:
31
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:3
Benign, no assertion criteria providedclinical testingNatera, Inc.Apr 06, 2018- -
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 01, 2021- -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17848068; hg19: chr1-76190216; API