rs1741949

Positions:

• chr3-197293064-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366207.1(DLG1):​c.151+3282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,996 control chromosomes in the GnomAD database, including 24,745 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 (24745 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.151+3282C>T		intron_variant		ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1	c.151+3282C>T		intron_variant			NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85748 AN: 151878 Hom.: 24739 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.564 AC: 85788 AN: 151996 Hom.: 24745 Cov.: 32 AF XY: 0.564 AC XY: 41891 AN XY: 74280

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.573

Alfa AF: 0.602 Hom.: 12667

Bravo AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1741949; hg19: chr3-197019935;