rs12964965

Variant names:

• chr18-3520557-T-C
• rs12964965
• NM_004746.4:c.2480-11896A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.2480-11896A>G		intron_variant	Intron 10 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.2480-11896A>G		intron_variant	Intron 10 of 12	5	NM_004746.4	ENSP00000316377.3

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

African (AFR) AF: 0.216 AC: 8959 AN: 41454

American (AMR) AF: 0.440 AC: 6715 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1593 AN: 5154

South Asian (SAS) AF: 0.226 AC: 1086 AN: 4810

European-Finnish (FIN) AF: 0.378 AC: 3985 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25583 AN: 67954

Other (OTH) AF: 0.320 AC: 673 AN: 2104

Alfa AF: 0.363 Hom.: 17578

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
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12964965; hg19: chr18-3520555;