rs2049161

Variant names:

• chr18-4127583-A-C
• rs2049161
• NM_004746.4:c.-159+23597T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-4127583-A-C
• chr18-4127583-A-T

Variant summary

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

The NM_004746.4(DLGAP1):​c.-159+23597T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,128 control chromosomes in the GnomAD database, including 3,944 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 0.22 (3944 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-159+23597T>G		intron_variant	Intron 2 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-159+23597T>G		intron_variant	Intron 2 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32850 AN: 152010 Hom.: 3940 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.216 AC: 32885 AN: 152128 Hom.: 3944 Cov.: 32 AF XY: 0.213 AC XY: 15840 AN XY: 74370

African (AFR) AF: 0.314 AC: 13041 AN: 41482

American (AMR) AF: 0.250 AC: 3820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.118 AC: 612 AN: 5182

South Asian (SAS) AF: 0.188 AC: 903 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1240 AN: 10592

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11733 AN: 67982

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.193 Hom.: 5473

Bravo AF: 0.232

Asia WGS AF: 0.128 AC: 447 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.57
PhyloP100		2.8
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: rs2049161; hg19: chr18-4127583;