chr17-7218466-T-C

Position:

• chr17-7218466-T-C

Variant summary

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

The ENST00000399510.8(DLG4):​c.118+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,458,246 control chromosomes in the GnomAD database, including 307,608 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 0.69 (36639 hom., cov: 32)
  • Exomes 𝑓: 0.64 (270969 hom.)
• Consequence: DLG4 ENST00000399510.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACADVL	NM_001270447.2	c.131+648T>C		intron_variant
DLG4	NM_001321074.1	c.118+75A>G		intron_variant
DLG4	NM_001365.4	c.118+75A>G		intron_variant
DLG4	NR_135527.1	n.1319+75A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG4	ENST00000399510.8	c.118+75A>G		intron_variant		1
ACADVL	ENST00000543245.6	c.131+648T>C		intron_variant		2
DLG4	ENST00000648172.8	c.118+75A>G		intron_variant
DLG4	ENST00000491753.2	c.118+75A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104837 AN: 151922 Hom.: 36581 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.642 AC: 839106 AN: 1306206 Hom.: 270969 Cov.: 21 AF XY: 0.644 AC XY: 417979 AN XY: 648950

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.680

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.690 AC: 104957 AN: 152040 Hom.: 36639 Cov.: 32 AF XY: 0.692 AC XY: 51432 AN XY: 74316

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.695

Alfa AF: 0.691 Hom.: 5899

Bravo AF: 0.689

Asia WGS AF: 0.693 AC: 2413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2521985; hg19: chr17-7121785; COSMIC: COSV57242211; COSMIC: COSV57242211;