rs474122

Positions:

• chr18-3603114-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.1592-20866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,034 control chromosomes in the GnomAD database, including 36,632 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 0.69 (36623 hom., cov: 31)
  • Exomes 𝑓: 0.83 (9 hom.)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765

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]

DLGAP1-AS2 (HGNC:28146): (DLGAP1 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.1592-20866T>C		intron_variant		ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.1592-20866T>C		intron_variant		5	NM_004746.4	ENSP00000316377	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104573 AN: 151892 Hom.: 36622 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.833 AC: 20 AN: 24 Hom.: 9 Cov.: 0 AF XY: 0.778 AC XY: 14 AN XY: 18

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.688 AC: 104597 AN: 152010 Hom.: 36623 Cov.: 31 AF XY: 0.693 AC XY: 51510 AN XY: 74290

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.689

Alfa AF: 0.725 Hom.: 22344

Bravo AF: 0.665

Asia WGS AF: 0.731 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.67

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: rs474122; hg19: chr18-3603112;