18-3546983-A-G

Variant names:

• chr18-3546983-A-G
• rs600173
• NM_004746.4:c.2058-12368T>C

Variant summary

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

The NM_001398525.1(DLGAP1):​c.2088-12368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,896 control chromosomes in the GnomAD database, including 25,974 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 0.53 (25974 hom., cov: 31)
• Consequence: DLGAP1 NM_001398525.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001398525.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.2058-12368T>C		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.2088-12368T>C		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.2088-12368T>C		intron	N/A	NP_001385455.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.2058-12368T>C		intron	N/A	ENSP00000316377.3
	DLGAP1	ENST00000400147.6	TSL:1	c.1152-12368T>C		intron	N/A	ENSP00000383011.2
	DLGAP1	ENST00000400145.6	TSL:1	c.1152-12368T>C		intron	N/A	ENSP00000383010.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80251 AN: 151778 Hom.: 25982 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.528 AC: 80240 AN: 151896 Hom.: 25974 Cov.: 31 AF XY: 0.535 AC XY: 39739 AN XY: 74254

African (AFR) AF: 0.135 AC: 5619 AN: 41472

American (AMR) AF: 0.631 AC: 9624 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2215 AN: 3468

East Asian (EAS) AF: 0.549 AC: 2842 AN: 5176

South Asian (SAS) AF: 0.646 AC: 3115 AN: 4824

European-Finnish (FIN) AF: 0.784 AC: 8189 AN: 10440

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46588 AN: 67954

Other (OTH) AF: 0.565 AC: 1189 AN: 2104

Alfa AF: 0.597 Hom.: 3296

Bravo AF: 0.502

Asia WGS AF: 0.545 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.15
Mutation Taster		=16/84	disease causing (long InDel)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs600173; hg19: chr18-3546981;