rs8083633

Positions:

• chr18-3522008-T-C

Variant summary

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

The NM_004746.4(DLGAP1):​c.2479+12186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,154 control chromosomes in the GnomAD database, including 1,977 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 0.15 (1977 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.2479+12186A>G		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.2479+12186A>G		intron_variant		5	NM_004746.4	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23068 AN: 152036 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.152 AC: 23074 AN: 152154 Hom.: 1977 Cov.: 32 AF XY: 0.147 AC XY: 10914 AN XY: 74388

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.141

Alfa AF: 0.183 Hom.: 5544

Bravo AF: 0.153

Asia WGS AF: 0.0750 AC: 263 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	1.8
DANN	Benign	0.64

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: rs8083633; hg19: chr18-3522006;