rs10502327

Variant names:

• chr18-4449347-T-C
• rs10502327
• NM_004746.4:c.-267+5659A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.-267+5659A>G		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.-267+5659A>G		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.-262+5659A>G		intron	N/A	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.-267+5659A>G		intron	N/A	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000581527.5	TSL:2	c.-267+5659A>G		intron	N/A	ENSP00000463864.1	O14490-7
	DLGAP1	ENST00000579652.1	TSL:5	n.17+5659A>G		intron	N/A

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

African (AFR) AF: 0.0770 AC: 3201 AN: 41552

American (AMR) AF: 0.211 AC: 3223 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3464

East Asian (EAS) AF: 0.176 AC: 910 AN: 5164

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1606 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8853 AN: 67990

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.126 Hom.: 194

Bravo AF: 0.130

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10502327; hg19: chr18-4449347;