1-75775709-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACADM Gene-Disease associations (from GenCC):

• medium chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.256 AC: 10629 AN: 41502

American (AMR) AF: 0.0511 AC: 781 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00768 AC: 37 AN: 4820

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2057 AN: 68000

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0737 Hom.: 137

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
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs1146611; hg19: chr1-76241394;