3-197047485-G-A

Variant names:

• chr3-197047485-G-A
• rs7638423
• NM_001366207.1:c.2576-2756C>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.2576-2756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,970 control chromosomes in the GnomAD database, including 9,779 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 0.33 (9779 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG1	NM_001366207.1	MANE Select	c.2576-2756C>T		intron	N/A	NP_001353136.1
	DLG1	NM_004087.2		c.2675-2756C>T		intron	N/A	NP_004078.2
	DLG1	NM_001366214.1		c.2672-2756C>T		intron	N/A	NP_001353143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG1	ENST00000667157.1	MANE Select	c.2576-2756C>T		intron	N/A	ENSP00000499414.1
	DLG1	ENST00000346964.6	TSL:1	c.2675-2756C>T		intron	N/A	ENSP00000345731.2
	DLG1	ENST00000419354.5	TSL:1	c.2609-2756C>T		intron	N/A	ENSP00000407531.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49656 AN: 151858 Hom.: 9782 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.327 AC: 49665 AN: 151970 Hom.: 9779 Cov.: 32 AF XY: 0.332 AC XY: 24629 AN XY: 74278

African (AFR) AF: 0.116 AC: 4804 AN: 41448

American (AMR) AF: 0.398 AC: 6084 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3718 AN: 5184

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4820

European-Finnish (FIN) AF: 0.432 AC: 4545 AN: 10532

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26706 AN: 67944

Other (OTH) AF: 0.329 AC: 692 AN: 2102

Alfa AF: 0.367 Hom.: 14618

Bravo AF: 0.320

Asia WGS AF: 0.457 AC: 1586 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		0.029
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: rs7638423; hg19: chr3-196774356;