chr17-7219921-T-TGGGCGTGCAGGACGCGGGCGTGCAGGACGC

Position:

• chr17-7219921-T-TGGGCGTGCAGGACGCGGGCGTGCAGGACGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000350303.9(ACADVL):​c.-49_-48insGGGCGTGCAGGACGCGGGCGTGCAGGACGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,555,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: ACADVL ENST00000350303.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

Genes affected

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

DLG4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADVL	NM_000018.4			upstream_gene_variant		ENST00000356839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACADVL	ENST00000356839.10			upstream_gene_variant		1	NM_000018.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151688 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000420 AC: 59 AN: 1403608 Hom.: 0 Cov.: 99 AF XY: 0.0000533 AC XY: 37 AN XY: 693858

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000824

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000342

Gnomad4 SAS exome AF: 0.000361

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000101

Gnomad4 OTH exome AF: 0.0000341

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151808 Hom.: 0 Cov.: 0 AF XY: 0.0000674 AC XY: 5 AN XY: 74214

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6145976; hg19: chr17-7123240;