chr17-7219921-T-TGGGCGTGCAGGACGC

Position:

• chr17-7219921-T-TGGGCGTGCAGGACGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000350303.9(ACADVL):​c.-63_-49dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,554,922 control chromosomes in the GnomAD database, including 250,780 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20943 hom., cov: 0)
  • Exomes 𝑓: 0.57 (229837 hom.)
• Consequence: ACADVL ENST00000350303.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 17-7219921-T-TGGGCGTGCAGGACGC is Benign according to our data. Variant chr17-7219921-T-TGGGCGTGCAGGACGC is described in ClinVar as [Benign]. Clinvar id is 166637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADVL	NM_000018.4			upstream_gene_variant		ENST00000356839.10	NP_000009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10			upstream_gene_variant		1	NM_000018.4	ENSP00000349297	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77778 AN: 151612 Hom.: 20921 Cov.: 0

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.569 AC: 798723 AN: 1403190 Hom.: 229837 Cov.: 99 AF XY: 0.572 AC XY: 396860 AN XY: 693630

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.513 AC: 77841 AN: 151732 Hom.: 20943 Cov.: 0 AF XY: 0.518 AC XY: 38438 AN XY: 74168

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.551

Alfa AF: 0.484 Hom.: 2208

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Very long chain acyl-CoA dehydrogenase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 03, 2014

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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;