3-197047485-G-A

Position:

• chr3-197047485-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.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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.2576-2756C>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.2576-2756C>T		intron_variant			NM_001366207.1	ENSP00000499414.1

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

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.329

Alfa AF: 0.375 Hom.: 11582

Bravo AF: 0.320

Asia WGS AF: 0.457 AC: 1586 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.59

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: rs7638423; hg19: chr3-196774356;