rs1146611

Variant names:

• chr1-75775709-G-A
• rs1146611
• ENST00000528016.1:n.*21+6467G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528016.1(ACADM):​n.*21+6467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,152 control chromosomes in the GnomAD database, including 1,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.092 (1403 hom., cov: 32)
• Consequence: ACADM ENST00000528016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADM	ENST00000528016.1	n.*21+6467G>A		intron_variant	Intron 3 of 4	4		ENSP00000434284.1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13944 AN: 152034 Hom.: 1403 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0918 AC: 13960 AN: 152152 Hom.: 1403 Cov.: 32 AF XY: 0.0888 AC XY: 6606 AN XY: 74364

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00768

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0797

Alfa AF: 0.0667 Hom.: 112

Bravo AF: 0.101

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1146611; hg19: chr1-76241394;