chr17-7217786-C-A

Position:

• chr17-7217786-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000399510.8(DLG4):​c.159+455G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,535,062 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (68 hom., cov: 30)
  • Exomes 𝑓: 0.032 (859 hom.)
• Consequence: DLG4 ENST00000399510.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.382

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-7217786-C-A is Benign according to our data. Variant chr17-7217786-C-A is described in ClinVar as [Benign]. Clinvar id is 2428699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7217786-C-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3626/152048) while in subpopulation NFE AF= 0.0361 (2450/67958). AF 95% confidence interval is 0.0349. There are 68 homozygotes in gnomad4. There are 1714 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3626 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADVL	NM_001270447.2	c.99C>A	p.Gly33=	synonymous_variant	2/21
DLG4	NM_001321074.1	c.159+455G>T		intron_variant
DLG4	NM_001365.4	c.159+455G>T		intron_variant
DLG4	NR_135527.1	n.1360+455G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG4	ENST00000399510.8	c.159+455G>T		intron_variant		1
ACADVL	ENST00000543245.6	c.99C>A	p.Gly33=	synonymous_variant	2/21	2
DLG4	ENST00000648172.8	c.159+455G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3614 AN: 151932 Hom.: 67 Cov.: 30

Gnomad AFR AF: 0.00738

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.0239 AC: 3067 AN: 128336 Hom.: 59 AF XY: 0.0250 AC XY: 1760 AN XY: 70276

Gnomad AFR exome AF: 0.00641

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.000288

Gnomad SAS exome AF: 0.0235

Gnomad FIN exome AF: 0.0202

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0302

GnomAD4 exome AF: 0.0319 AC: 44163 AN: 1383014 Hom.: 859 Cov.: 31 AF XY: 0.0318 AC XY: 21686 AN XY: 682426

Gnomad4 AFR exome AF: 0.00630

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.0245

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0238 AC: 3626 AN: 152048 Hom.: 68 Cov.: 30 AF XY: 0.0231 AC XY: 1714 AN XY: 74314

Gnomad4 AFR AF: 0.00770

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0302 Hom.: 19

Bravo AF: 0.0227

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Very long chain acyl-CoA dehydrogenase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72839706; hg19: chr17-7121105;