rs2017365

Variant names:

• chr17-7219305-G-A
• rs2017365
• ENST00000648172.8:c.-456C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365.5(DLG4):​c.-456C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 757,688 control chromosomes in the GnomAD database, including 139,323 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 0.55 (24134 hom., cov: 31)
  • Exomes 𝑓: 0.61 (115189 hom.)
• Consequence: DLG4 NM_001365.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001365.5	c.-456C>T		5_prime_UTR_variant	Exon 1 of 22		NP_001356.1
DLG4	NM_001321074.1	c.-456C>T		5_prime_UTR_variant	Exon 1 of 22		NP_001308003.1
ACADVL	NM_001270447.2	c.132-817G>A		intron_variant	Intron 2 of 20		NP_001257376.1
DLG4	NR_135527.1	n.746C>T		non_coding_transcript_exon_variant	Exon 1 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000648172.8	c.-456C>T		5_prime_UTR_variant	Exon 1 of 22			ENSP00000497806.3
DLG4	ENST00000491753.2	n.-456C>T		non_coding_transcript_exon_variant	Exon 1 of 21	2		ENSP00000467897.2
DLG4	ENST00000491753.2	n.-456C>T		5_prime_UTR_variant	Exon 1 of 21	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83679 AN: 151780 Hom.: 24109 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.613 AC: 371530 AN: 605790 Hom.: 115189 Cov.: 8 AF XY: 0.614 AC XY: 175814 AN XY: 286184

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.551 AC: 83746 AN: 151898 Hom.: 24134 Cov.: 31 AF XY: 0.555 AC XY: 41214 AN XY: 74220

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.588

Alfa AF: 0.621 Hom.: 27640

Bravo AF: 0.531

Asia WGS AF: 0.570 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2017365; hg19: chr17-7122624;