NM_004746.4:c.2480-3557A>G

Variant names:

• chr18-3512218-T-C
• rs17724172
• NM_004746.4:c.2480-3557A>G

Variant summary

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

The NM_004746.4(DLGAP1):​c.2480-3557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,146 control chromosomes in the GnomAD database, including 2,274 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 0.17 (2274 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. 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.2480-3557A>G		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.2510-3557A>G		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.2510-3557A>G		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.2480-3557A>G		intron	N/A	ENSP00000316377.3
	DLGAP1	ENST00000400147.6	TSL:1	c.1574-3557A>G		intron	N/A	ENSP00000383011.2
	DLGAP1	ENST00000400145.6	TSL:1	c.1574-3557A>G		intron	N/A	ENSP00000383010.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25190 AN: 152028 Hom.: 2277 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.166 AC: 25186 AN: 152146 Hom.: 2274 Cov.: 32 AF XY: 0.169 AC XY: 12575 AN XY: 74392

African (AFR) AF: 0.0992 AC: 4119 AN: 41516

American (AMR) AF: 0.159 AC: 2430 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3464

East Asian (EAS) AF: 0.130 AC: 672 AN: 5182

South Asian (SAS) AF: 0.255 AC: 1231 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10576

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13034 AN: 67980

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.183 Hom.: 8634

Bravo AF: 0.160

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		0.068
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: rs17724172; hg19: chr18-3512216;