chr3-197289869-C-T

Variant names:

• chr3-197289869-C-T
• rs382579
• NM_001366207.1:c.151+6477G>A

Variant summary

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

The NM_001366207.1(DLG1):​c.151+6477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,102 control chromosomes in the GnomAD database, including 41,347 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 0.74 (41347 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 2 publications found

Genes affected

DLG1 (HGNC:2900): (discs large MAGUK scaffold protein 1) This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]

DLG1 Gene-Disease associations (from GenCC):

• Brugada syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366207.1. 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
	DLG1	NM_001366207.1	MANE Select	c.151+6477G>A		intron	N/A	NP_001353136.1	Q12959-4
	DLG1	NM_004087.2		c.151+6477G>A		intron	N/A	NP_004078.2	Q12959-2
	DLG1	NM_001366214.1		c.151+6477G>A		intron	N/A	NP_001353143.1	A0A590UJD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG1	ENST00000667157.1	MANE Select	c.151+6477G>A		intron	N/A	ENSP00000499414.1	Q12959-4
	DLG1	ENST00000346964.6	TSL:1	c.151+6477G>A		intron	N/A	ENSP00000345731.2	Q12959-2
	DLG1	ENST00000419354.5	TSL:1	c.151+6477G>A		intron	N/A	ENSP00000407531.1	Q12959-1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111942 AN: 151984 Hom.: 41315 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.737 AC: 112025 AN: 152102 Hom.: 41347 Cov.: 32 AF XY: 0.736 AC XY: 54725 AN XY: 74376

African (AFR) AF: 0.719 AC: 29848 AN: 41498

American (AMR) AF: 0.714 AC: 10914 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2643 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4225 AN: 5174

South Asian (SAS) AF: 0.763 AC: 3680 AN: 4826

European-Finnish (FIN) AF: 0.704 AC: 7423 AN: 10548

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50800 AN: 67990

Other (OTH) AF: 0.732 AC: 1544 AN: 2110

Alfa AF: 0.748 Hom.: 5538

Bravo AF: 0.737

Asia WGS AF: 0.771 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.33
PhyloP100		0.28
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: rs382579; hg19: chr3-197016740;