rs280984

Positions:

• chr18-4451130-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.-267+3876G>A		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-267+3876G>A		intron_variant		5	NM_004746.4	P1
DLGAP1	ENST00000581527.5	c.-267+3876G>A		intron_variant		2
DLGAP1	ENST00000579652.1	n.17+3876G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.361

Alfa AF: 0.372 Hom.: 19253

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

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: rs280984; hg19: chr18-4451130;