17-7219921-T-TGGGCGTGCAGGACGC

Variant names:

• chr17-7219921-T-TGGGCGTGCAGGACGC
• rs6145976
• ENST00000350303:c.-63_-49dupGGGCGTGCAGGACGC

Variant summary

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

The NM_001321074.1(DLG4):​c.-1087_-1073dupGCGTCCTGCACGCCC 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: DLG4 NM_001321074.1 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:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
ACADVL	NM_000018.4	c.-64_-63insGGGCGTGCAGGACGC		upstream_gene_variant		ENST00000356839.10	NP_000009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10	c.-64_-63insGGGCGTGCAGGACGC		upstream_gene_variant		1	NM_000018.4	ENSP00000349297.5
DLG4	ENST00000648172.8	c.-1087_-1073dupGCGTCCTGCACGCCC		upstream_gene_variant				ENSP00000497806.3
DLG4	ENST00000491753.2	n.-1087_-1073dupGCGTCCTGCACGCCC		upstream_gene_variant		2		ENSP00000467897.2

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 03, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;