rs6805920

Variant names:

• chr3-197235458-A-C
• rs6805920
• NM_001366207.1:c.319-40869T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-197235458-A-C
• chr3-197235458-A-T

Variant summary

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

The NM_001366207.1(DLG1):​c.319-40869T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,178 control chromosomes in the GnomAD database, including 7,437 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 0.28 (7437 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.319-40869T>G		intron_variant	Intron 4 of 24	ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1	c.319-40869T>G		intron_variant	Intron 4 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43202 AN: 152060 Hom.: 7438 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.284 AC: 43217 AN: 152178 Hom.: 7437 Cov.: 32 AF XY: 0.288 AC XY: 21416 AN XY: 74396

African (AFR) AF: 0.111 AC: 4629 AN: 41552

American (AMR) AF: 0.348 AC: 5323 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3691 AN: 5172

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3925 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22376 AN: 67982

Other (OTH) AF: 0.276 AC: 581 AN: 2108

Alfa AF: 0.315 Hom.: 31149

Bravo AF: 0.277

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.52
PhyloP100		0.93
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: rs6805920; hg19: chr3-196962329;