rs739669

Positions:

• chr17-7219058-G-A
• chr17-7219058-G-C
• chr17-7219058-G-T

Variant summary

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

The ENST00000399510.8(DLG4):​c.-209C>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 0.668 in 615,860 control chromosomes in the GnomAD database, including 138,929 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 0.70 (38420 hom., cov: 31)
  • Exomes 𝑓: 0.66 (100509 hom.)
• Consequence: DLG4 ENST00000399510.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG4	NM_001321074.1	c.-209C>T		5_prime_UTR_variant	1/22		NP_001308003.1
DLG4	NM_001365.4	c.-209C>T		5_prime_UTR_variant	1/22		NP_001356.1
ACADVL	NM_001270447.2	c.132-1064G>A		intron_variant			NP_001257376.1
DLG4	NR_135527.1	n.993C>T		non_coding_transcript_exon_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399510.8	c.-209C>T		5_prime_UTR_variant	1/22	1		ENSP00000382428
DLG4	ENST00000648172.8	c.-209C>T		5_prime_UTR_variant	1/22			ENSP00000497806
ACADVL	ENST00000543245.6	c.132-1064G>A		intron_variant		2		ENSP00000438689
DLG4	ENST00000491753.2	c.-209C>T		5_prime_UTR_variant, NMD_transcript_variant	1/21	2		ENSP00000467897

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106992 AN: 151918 Hom.: 38347 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.656 AC: 304268 AN: 463824 Hom.: 100509 Cov.: 5 AF XY: 0.657 AC XY: 160980 AN XY: 245074

Gnomad4 AFR exome AF: 0.854

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.641

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.705 AC: 107131 AN: 152036 Hom.: 38420 Cov.: 31 AF XY: 0.705 AC XY: 52404 AN XY: 74298

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.707

Alfa AF: 0.652 Hom.: 28520

Bravo AF: 0.706

Asia WGS AF: 0.692 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs739669; hg19: chr17-7122377;