18-3850002-A-G

Variant summary

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

The NM_004746.4(DLGAP1):c.957+29110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,854 control chromosomes in the GnomAD database, including 6,667 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 0.29 (6667 hom., cov: 31)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.957+29110T>C		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.957+29110T>C		intron_variant		5	NM_004746.4	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44573 AN: 151736 Hom.: 6656 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.294 AC: 44604 AN: 151854 Hom.: 6667 Cov.: 31 AF XY: 0.295 AC XY: 21926 AN XY: 74222

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.272

Alfa AF: 0.286 Hom.: 1056

Bravo AF: 0.295

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.5
Dann	Benign	0.77

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: rs7245298; hg19: chr18-3850002;