rs10502327

Positions:

• chr18-4449347-T-C

Variant summary

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

The NM_004746.4(DLGAP1):​c.-267+5659A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,200 control chromosomes in the GnomAD database, including 1,479 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 0.13 (1479 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.-267+5659A>G		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-267+5659A>G		intron_variant		5	NM_004746.4	P1
DLGAP1	ENST00000581527.5	c.-267+5659A>G		intron_variant		2
DLGAP1	ENST00000579652.1	n.17+5659A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19743 AN: 152082 Hom.: 1479 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.130 AC: 19750 AN: 152200 Hom.: 1479 Cov.: 32 AF XY: 0.134 AC XY: 9963 AN XY: 74412

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.132

Alfa AF: 0.128 Hom.: 188

Bravo AF: 0.130

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10502327; hg19: chr18-4449347;