rs17203281

Variant names:

• chr17-7196492-G-A
• rs17203281
• NM_001321075.3:c.1167C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7196492-G-A
• chr17-7196492-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001321075.3(DLG4):​c.1167C>T​(p.Ile389Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,368 control chromosomes in the GnomAD database, including 77,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6382 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70993 hom.)
• Consequence: DLG4 NM_001321075.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.74

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-7196492-G-A is Benign according to our data. Variant chr17-7196492-G-A is described in ClinVar as [Benign]. Clinvar id is 1255506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.1167C>T	p.Ile389Ile	synonymous_variant	Exon 10 of 20	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.1167C>T	p.Ile389Ile	synonymous_variant	Exon 10 of 20	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.8	c.1296C>T	p.Ile432Ile	synonymous_variant	Exon 12 of 22			ENSP00000497806.3
DLG4	ENST00000648896.1	c.1266C>T	p.Ile422Ile	synonymous_variant	Exon 10 of 20			ENSP00000497546.1
DLG4	ENST00000649520.1	c.987C>T	p.Ile329Ile	synonymous_variant	Exon 9 of 19			ENSP00000497647.1
DLG4	ENST00000648263.1	c.987C>T	p.Ile329Ile	synonymous_variant	Exon 8 of 14			ENSP00000498035.1
DLG4	ENST00000491753.2	n.1296C>T		non_coding_transcript_exon_variant	Exon 12 of 21	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42701 AN: 151992 Hom.: 6380 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.283 AC: 70531 AN: 249188 Hom.: 10847 AF XY: 0.286 AC XY: 38690 AN XY: 135178

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.312

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.307 AC: 449018 AN: 1461258 Hom.: 70993 Cov.: 39 AF XY: 0.306 AC XY: 222099 AN XY: 726908

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.281 AC: 42707 AN: 152110 Hom.: 6382 Cov.: 32 AF XY: 0.281 AC XY: 20898 AN XY: 74360

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.296

Alfa AF: 0.310 Hom.: 12413

Bravo AF: 0.264

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual developmental disorder 62 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

DLG4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs17203281; hg19: chr17-7099811; COSMIC: COSV57236265; COSMIC: COSV57236265;