rs4916461

Positions:

• chr3-197171738-C-A
• chr3-197171738-C-G
• chr3-197171738-C-T

Variant summary

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

The NM_001366207.1(DLG1):​c.484-21942G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,876 control chromosomes in the GnomAD database, including 12,447 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 0.40 (12447 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.484-21942G>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.484-21942G>T		intron_variant			NM_001366207.1	ENSP00000499414

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60007 AN: 151758 Hom.: 12445 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.395 AC: 60043 AN: 151876 Hom.: 12447 Cov.: 32 AF XY: 0.399 AC XY: 29624 AN XY: 74252

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.381

Alfa AF: 0.405 Hom.: 21104

Bravo AF: 0.393

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4916461; hg19: chr3-196898609;