17-7192188-C-T

Position:

• chr17-7192188-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001321075.3(DLG4):​c.1867-186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 435,494 control chromosomes in the GnomAD database, including 36,753 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 0.39 (11612 hom., cov: 29)
  • Exomes 𝑓: 0.42 (25141 hom.)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.1867-186G>A		intron_variant		ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.1867-186G>A		intron_variant		2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.8	c.1996-186G>A		intron_variant				ENSP00000497806.3
DLG4	ENST00000648896.1	c.1966-186G>A		intron_variant				ENSP00000497546.1
DLG4	ENST00000649520.1	c.1687-186G>A		intron_variant				ENSP00000497647.1
DLG4	ENST00000491753.2	n.1995+757G>A		intron_variant		2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58260 AN: 151186 Hom.: 11595 Cov.: 29

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.417 AC: 118431 AN: 284190 Hom.: 25141 Cov.: 2 AF XY: 0.419 AC XY: 61487 AN XY: 146838

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.391

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.385 AC: 58313 AN: 151304 Hom.: 11612 Cov.: 29 AF XY: 0.385 AC XY: 28431 AN XY: 73898

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.407

Alfa AF: 0.387 Hom.: 4269

Bravo AF: 0.377

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242449; hg19: chr17-7095507;