rs11662259

Positions:

• chr18-3582274-A-C

Variant summary

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

The NM_004746.4(DLGAP1):​c.1592-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,591,570 control chromosomes in the GnomAD database, including 29,276 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 0.18 (2526 hom., cov: 31)
  • Exomes 𝑓: 0.19 (26750 hom.)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.1592-26T>G		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.1592-26T>G		intron_variant		5	NM_004746.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27445 AN: 151812 Hom.: 2523 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.195 AC: 46947 AN: 240832 Hom.: 4719 AF XY: 0.200 AC XY: 26136 AN XY: 130682

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.262

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.190 AC: 274168 AN: 1439640 Hom.: 26750 Cov.: 34 AF XY: 0.193 AC XY: 137926 AN XY: 713680

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.181 AC: 27486 AN: 151930 Hom.: 2526 Cov.: 31 AF XY: 0.181 AC XY: 13445 AN XY: 74248

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.201

Alfa AF: 0.191 Hom.: 3035

Bravo AF: 0.185

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11662259; hg19: chr18-3582272; COSMIC: COSV59807571; COSMIC: COSV59807571;