18-3589109-A-G

Variant names:

• chr18-3589109-A-G
• rs2314028
• NM_004746.4:c.1592-6861T>C

Variant summary

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

The NM_004746.4(DLGAP1):​c.1592-6861T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 149,044 control chromosomes in the GnomAD database, including 69 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 0.016 (69 hom., cov: 33)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.1592-6861T>C		intron_variant	Intron 7 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.1592-6861T>C		intron_variant	Intron 7 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2312 AN: 148928 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00698

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000194

Gnomad OTH AF: 0.0108

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

GnomAD4 genome AF: 0.0156 AC: 2318 AN: 149044 Hom.: 69 Cov.: 33 AF XY: 0.0145 AC XY: 1056 AN XY: 72794

African (AFR) AF: 0.0537 AC: 2176 AN: 40490

American (AMR) AF: 0.00697 AC: 104 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4880

South Asian (SAS) AF: 0.000430 AC: 2 AN: 4656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000194 AC: 13 AN: 67028

Other (OTH) AF: 0.0107 AC: 22 AN: 2054

Alfa AF: 0.00974 Hom.: 5

Bravo AF: 0.0176

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		0.30
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: rs2314028; hg19: chr18-3589107;