rs280983

Variant names:

• chr18-4451489-T-C
• rs280983
• NM_004746.4:c.-267+3517A>G

Variant summary

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

The NM_004746.4(DLGAP1):​c.-267+3517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,988 control chromosomes in the GnomAD database, including 12,185 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 0.40 (12185 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-267+3517A>G		intron_variant	Intron 1 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-267+3517A>G		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-267+3517A>G		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000579652.1	n.17+3517A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60349 AN: 151870 Hom.: 12173 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.397 AC: 60390 AN: 151988 Hom.: 12185 Cov.: 32 AF XY: 0.395 AC XY: 29373 AN XY: 74272

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.427

Alfa AF: 0.393 Hom.: 3175

Bravo AF: 0.406

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.75

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: rs280983; hg19: chr18-4451489;