rs4916461

Variant names:

• chr3-197171738-C-A
• rs4916461
• NM_001366207.1:c.484-21942G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-197171738-C-A
• chr3-197171738-C-G
• chr3-197171738-C-T

Variant summary

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

The NM_004087.2(DLG1):​c.484-10000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,876 control chromosomes in the GnomAD database, including 12,447 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 0.40 (12447 hom., cov: 32)
• Consequence: DLG1 NM_004087.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004087.2. 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.484-21942G>T		intron	N/A	NP_001353136.1
	DLG1	NM_004087.2		c.484-10000G>T		intron	N/A	NP_004078.2
	DLG1	NM_001366214.1		c.484-10000G>T		intron	N/A	NP_001353143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG1	ENST00000667157.1	MANE Select	c.484-21942G>T		intron	N/A	ENSP00000499414.1
	DLG1	ENST00000346964.6	TSL:1	c.484-10000G>T		intron	N/A	ENSP00000345731.2
	DLG1	ENST00000419354.5	TSL:1	c.484-10000G>T		intron	N/A	ENSP00000407531.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60007 AN: 151758 Hom.: 12445 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.395 AC: 60043 AN: 151876 Hom.: 12447 Cov.: 32 AF XY: 0.399 AC XY: 29624 AN XY: 74252

African (AFR) AF: 0.300 AC: 12401 AN: 41388

American (AMR) AF: 0.426 AC: 6499 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3809 AN: 5176

South Asian (SAS) AF: 0.333 AC: 1603 AN: 4814

European-Finnish (FIN) AF: 0.453 AC: 4788 AN: 10560

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28395 AN: 67904

Other (OTH) AF: 0.381 AC: 805 AN: 2112

Alfa AF: 0.403 Hom.: 33498

Bravo AF: 0.393

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.65
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4916461; hg19: chr3-196898609;