rs8092654

Positions:

• chr18-3956145-C-T

Variant summary

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

The NM_004746.4(DLGAP1):​c.-73+48971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,016 control chromosomes in the GnomAD database, including 477 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 0.054 (477 hom., cov: 33)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.-73+48971G>A		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-73+48971G>A		intron_variant		5	NM_004746.4	P1
DLGAP1	ENST00000581527.5	c.-73+48971G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8189 AN: 151898 Hom.: 472 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00604

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0596

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

GnomAD4 genome AF: 0.0540 AC: 8212 AN: 152016 Hom.: 477 Cov.: 33 AF XY: 0.0538 AC XY: 3994 AN XY: 74302

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00605

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0589

Alfa AF: 0.0393 Hom.: 95

Bravo AF: 0.0595

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.086
DANN	Benign	0.50

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: rs8092654; hg19: chr18-3956145;