rs280984

Variant names:

• chr18-4451130-C-T
• rs280984
• NM_004746.4:c.-267+3876G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004746.4(DLGAP1):​c.-267+3876G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,028 control chromosomes in the GnomAD database, including 8,343 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 0.32 (8343 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-267+3876G>A		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+3876G>A		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-267+3876G>A		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000579652.1	n.17+3876G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48890 AN: 151910 Hom.: 8345 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.322 AC: 48895 AN: 152028 Hom.: 8343 Cov.: 32 AF XY: 0.321 AC XY: 23820 AN XY: 74300

African (AFR) AF: 0.214 AC: 8884 AN: 41500

American (AMR) AF: 0.336 AC: 5133 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1893 AN: 5164

South Asian (SAS) AF: 0.418 AC: 2011 AN: 4814

European-Finnish (FIN) AF: 0.284 AC: 3002 AN: 10566

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25381 AN: 67930

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.359 Hom.: 30514

Bravo AF: 0.321

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.68
DANN	Benign	0.74
PhyloP100		-1.4
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: rs280984; hg19: chr18-4451130;