rs12964965

chr18-3520557-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.2480-11896A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,974 control chromosomes in the GnomAD database, including 8,873 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 (8873 hom., cov: 31)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500

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 (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.2480-11896A>G		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.2480-11896A>G		intron_variant		5	NM_004746.4	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50100 AN: 151854 Hom.: 8872 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.330 AC: 50119 AN: 151974 Hom.: 8873 Cov.: 31 AF XY: 0.328 AC XY: 24340 AN XY: 74292

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.320

Alfa AF: 0.366 Hom.: 14102

Bravo AF: 0.331

Asia WGS AF: 0.282 AC: 983 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	4.5
Dann	Benign	0.43

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: rs12964965; hg19: chr18-3520555;