NM_001365.5:c.-209C>T

Variant names:

• chr17-7219058-G-A
• rs739669
• NM_001365.5:c.-209C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365.5(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 NM_001365.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 30 publications found

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]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NM_001365.5	MANE Plus Clinical	c.-209C>T		5_prime_UTR	Exon 1 of 22	NP_001356.1	P78352-2
	DLG4	NM_001321074.1		c.-209C>T		5_prime_UTR	Exon 1 of 22	NP_001308003.1	B9EGL1
	ACADVL	NM_001270447.2		c.132-1064G>A		intron	N/A	NP_001257376.1	P49748-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.-209C>T		5_prime_UTR	Exon 1 of 22	ENSP00000497806.3	P78352-2
	DLG4	ENST00000399510.8	TSL:1	c.-209C>T		5_prime_UTR	Exon 1 of 22	ENSP00000382428.3	B9EGL1
	DLG4	ENST00000491753.2	TSL:2	n.-209C>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000467897.2	B7Z3U2

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

African (AFR) AF: 0.854 AC: 10949 AN: 12820

American (AMR) AF: 0.602 AC: 12416 AN: 20612

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 8963 AN: 13982

East Asian (EAS) AF: 0.645 AC: 19935 AN: 30918

South Asian (SAS) AF: 0.670 AC: 31057 AN: 46386

European-Finnish (FIN) AF: 0.677 AC: 20060 AN: 29628

Middle Eastern (MID) AF: 0.770 AC: 1681 AN: 2184

European-Non Finnish (NFE) AF: 0.647 AC: 181619 AN: 280854

Other (OTH) AF: 0.665 AC: 17588 AN: 26440

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

African (AFR) AF: 0.845 AC: 35040 AN: 41472

American (AMR) AF: 0.643 AC: 9814 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3466

East Asian (EAS) AF: 0.654 AC: 3359 AN: 5136

South Asian (SAS) AF: 0.667 AC: 3210 AN: 4812

European-Finnish (FIN) AF: 0.701 AC: 7413 AN: 10576

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43814 AN: 67984

Other (OTH) AF: 0.707 AC: 1493 AN: 2112

Alfa AF: 0.662 Hom.: 39753

Bravo AF: 0.706

Asia WGS AF: 0.692 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.54
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs739669; hg19: chr17-7122377;