3-197227576-T-G

Variant names:

• chr3-197227576-T-G
• rs2122824
• NM_001366207.1:c.319-32987A>C

Variant summary

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

The NM_001366207.1(DLG1):​c.319-32987A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,072 control chromosomes in the GnomAD database, including 24,619 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 0.56 (24619 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.319-32987A>C		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.319-32987A>C		intron_variant	Intron 4 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85518 AN: 151954 Hom.: 24613 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.563 AC: 85558 AN: 152072 Hom.: 24619 Cov.: 32 AF XY: 0.562 AC XY: 41747 AN XY: 74344

African (AFR) AF: 0.446 AC: 18478 AN: 41446

American (AMR) AF: 0.591 AC: 9031 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4081 AN: 5180

South Asian (SAS) AF: 0.704 AC: 3397 AN: 4826

European-Finnish (FIN) AF: 0.524 AC: 5538 AN: 10562

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 41007 AN: 67982

Other (OTH) AF: 0.568 AC: 1199 AN: 2110

Alfa AF: 0.486 Hom.: 1925

Bravo AF: 0.562

Asia WGS AF: 0.700 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.63
PhyloP100		-0.15
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: rs2122824; hg19: chr3-196954447;