rs12455524

Positions:

• chr18-3597527-G-A

Variant summary

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

The NM_004746.4(DLGAP1):​c.1592-15279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 310,440 control chromosomes in the GnomAD database, including 1,513 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 0.082 (648 hom., cov: 32)
  • Exomes 𝑓: 0.098 (865 hom.)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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]

DLGAP1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.1592-15279C>T		intron_variant		ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.1592-15279C>T		intron_variant		5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12431 AN: 152040 Hom.: 649 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0980 AC: 15519 AN: 158282 Hom.: 865 Cov.: 0 AF XY: 0.0997 AC XY: 8752 AN XY: 87794

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.0934

GnomAD4 genome AF: 0.0818 AC: 12441 AN: 152158 Hom.: 648 Cov.: 32 AF XY: 0.0815 AC XY: 6063 AN XY: 74372

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0999 Hom.: 1096

Bravo AF: 0.0840

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.98
DANN	Benign	0.65

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: rs12455524; hg19: chr18-3597525;