Genetic Variant DLGAP1:c.1592-26T>G (chr18-3582274-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004746.4(DLGAP1):c.1592-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,591,570 control chromosomes in the GnomAD database, including 29,276 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 0.18 ( 2526 hom., cov: 31)

Exomes 𝑓: 0.19 ( 26750 hom. )

Consequence

DLGAP1
NM_004746.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.776

Publications

6 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4 link	c.1592-26T>G		intron_variant	Intron 7 of 12	ENST00000315677.8	NP_004737.2	O14490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8 link	c.1592-26T>G		intron_variant	Intron 7 of 12	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27445

AN:

151812

Hom.:

2523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.201

GnomAD2 exomes

AF:

0.195

AC:

46947

AN:

240832

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.190

AC:

274168

AN:

1439640

Hom.:

26750

Cov.:

AF XY:

0.193

AC XY:

137926

AN XY:

713680

show subpopulations

African (AFR)

AF:

0.172

AC:

5609

AN:

32596

American (AMR)

AF:

0.200

AC:

8403

AN:

42058

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5629

AN:

25234

East Asian (EAS)

AF:

0.151

AC:

5935

AN:

39322

South Asian (SAS)

AF:

0.264

AC:

22549

AN:

85540

European-Finnish (FIN)

AF:

0.156

AC:

7879

AN:

50614

Middle Eastern (MID)

AF:

0.275

AC:

1553

AN:

5640

European-Non Finnish (NFE)

AF:

0.187

AC:

205056

AN:

1099288

Other (OTH)

AF:

0.195

AC:

11555

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

10619

21237

31856

42474

53093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7444

14888

22332

29776

37220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.181

AC:

27486

AN:

151930

Hom.:

2526

Cov.:

AF XY:

0.181

AC XY:

13445

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.168

AC:

6974

AN:

41436

American (AMR)

AF:

0.183

AC:

2791

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

780

AN:

3468

East Asian (EAS)

AF:

0.175

AC:

905

AN:

5158

South Asian (SAS)

AF:

0.257

AC:

1234

AN:

4810

European-Finnish (FIN)

AF:

0.160

AC:

1689

AN:

10548

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12572

AN:

67934

Other (OTH)

AF:

0.201

AC:

423

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1138

2275

3413

4550

5688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.189

Hom.:

3565

Bravo

AF:

0.185

Asia WGS

AF:

0.204

AC:

710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.40

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over