rs375577

Variant names:

• chr18-3683361-C-T
• rs375577
• NM_004746.4:c.1591+45774G>A

Variant summary

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

The NM_004746.4(DLGAP1):​c.1591+45774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,978 control chromosomes in the GnomAD database, including 6,264 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 0.26 (6264 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.1591+45774G>A		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.1591+45774G>A		intron_variant	Intron 7 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39406 AN: 151860 Hom.: 6245 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.260 AC: 39470 AN: 151978 Hom.: 6264 Cov.: 32 AF XY: 0.259 AC XY: 19225 AN XY: 74316

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.229

Alfa AF: 0.216 Hom.: 839

Bravo AF: 0.261

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.18

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: rs375577; hg19: chr18-3683361;