NM_001365.5:c.917-921G>A

Variant names:

• chr17-7197973-C-T
• rs3826408
• NM_001365.5:c.917-921G>A

Variant summary

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

The NM_001365.5(DLG4):​c.917-921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,924 control chromosomes in the GnomAD database, including 14,349 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 0.43 (14349 hom., cov: 31)
• Consequence: DLG4 NM_001365.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811
• 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]

DLG4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder 62

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 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.917-921G>A		intron	N/A	NP_001356.1
	DLG4	NM_001321075.3	MANE Select	c.788-921G>A		intron	N/A	NP_001308004.1
	DLG4	NM_001321074.1		c.908-921G>A		intron	N/A	NP_001308003.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.917-921G>A		intron	N/A	ENSP00000497806.3
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.788-921G>A		intron	N/A	ENSP00000382425.2
	DLG4	ENST00000399510.8	TSL:1	c.908-921G>A		intron	N/A	ENSP00000382428.3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65186 AN: 151806 Hom.: 14331 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.429 AC: 65235 AN: 151924 Hom.: 14349 Cov.: 31 AF XY: 0.431 AC XY: 31968 AN XY: 74236

African (AFR) AF: 0.349 AC: 14446 AN: 41422

American (AMR) AF: 0.419 AC: 6395 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2125 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4816

European-Finnish (FIN) AF: 0.520 AC: 5472 AN: 10522

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31944 AN: 67932

Other (OTH) AF: 0.443 AC: 938 AN: 2116

Alfa AF: 0.449 Hom.: 39841

Bravo AF: 0.415

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.66
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3826408; hg19: chr17-7101292;