17-7219637-G-T

Variant names:

• chr17-7219637-G-T
• rs79809891
• ENST00000491753.2:n.-788C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000491753.2(DLG4):​n.-788C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,087,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: DLG4 ENST00000491753.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 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: G2P, Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NR_135527.1	n.414C>A		non_coding_transcript_exon_variant	Exon 1 of 21
DLG4	NM_001365.5	c.-788C>A		5_prime_UTR_variant	Exon 1 of 22		NP_001356.1
DLG4	NM_001321074.1	c.-788C>A		5_prime_UTR_variant	Exon 1 of 22		NP_001308003.1
ACADVL	NM_001270447.2	c.132-485G>T		intron_variant	Intron 2 of 20		NP_001257376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000491753.2	n.-788C>A		non_coding_transcript_exon_variant	Exon 1 of 21	2		ENSP00000467897.2
DLG4	ENST00000648172.9	c.-788C>A		5_prime_UTR_variant	Exon 1 of 22			ENSP00000497806.3
DLG4	ENST00000491753.2	n.-788C>A		5_prime_UTR_variant	Exon 1 of 21	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1087422 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 519004

African (AFR) AF: 0.00 AC: 0 AN: 22984

American (AMR) AF: 0.00 AC: 0 AN: 12782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12532

East Asian (EAS) AF: 0.00 AC: 0 AN: 18450

South Asian (SAS) AF: 0.00 AC: 0 AN: 50840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2724

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 911272

Other (OTH) AF: 0.00 AC: 0 AN: 42232

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.52
PhyloP100		1.4
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs79809891; hg19: chr17-7122956;