3-197235458-A-C

Position:

• chr3-197235458-A-C

Variant summary

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

The NM_001366207.1(DLG1):​c.319-40869T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,178 control chromosomes in the GnomAD database, including 7,437 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 0.28 (7437 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG1	NM_001366207.1	c.319-40869T>G		intron_variant		ENST00000667157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG1	ENST00000667157.1	c.319-40869T>G		intron_variant			NM_001366207.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43202 AN: 152060 Hom.: 7438 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.284 AC: 43217 AN: 152178 Hom.: 7437 Cov.: 32 AF XY: 0.288 AC XY: 21416 AN XY: 74396

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.276

Alfa AF: 0.317 Hom.: 13666

Bravo AF: 0.277

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.52

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: rs6805920; hg19: chr3-196962329;