dbSNP rs988920: DLGAP1:c.-73+11129A>G (chr18-3993987-T-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.-73+11129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,020 control chromosomes in the GnomAD database, including 5,870 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 0.27 ( 5870 hom., cov: 32)

Consequence

DLGAP1
NM_004746.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0540

Publications

1 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:

DLGAP1-AS4 (HGNC:44333): (DLGAP1 antisense RNA 4)

DLGAP1-AS4 links:

Genome browser will be placed here

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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DLGAP1	NM_004746.4	MANE Select	c.-73+11129A>G	intron	N/A	NP_004737.2
DLGAP1	NM_001398525.1		c.-73+11129A>G	intron	N/A	NP_001385454.1
DLGAP1	NM_001398526.1		c.-73+11129A>G	intron	N/A	NP_001385455.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.-73+11129A>G	intron	N/A	ENSP00000316377.3	O14490-1
DLGAP1	ENST00000581550.5	TSL:1	n.324-7771A>G	intron	N/A
DLGAP1	ENST00000581527.5	TSL:2	c.-73+11129A>G	intron	N/A	ENSP00000463864.1	O14490-7

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41746

AN:

151902

Hom.:

5864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.292

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

GnomAD4 genome

AF:

0.275

AC:

41770

AN:

152020

Hom.:

5870

Cov.:

AF XY:

0.274

AC XY:

20405

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.259

AC:

10734

AN:

41480

American (AMR)

AF:

0.349

AC:

5338

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1184

AN:

3468

East Asian (EAS)

AF:

0.254

AC:

1313

AN:

5166

South Asian (SAS)

AF:

0.322

AC:

1541

AN:

4786

European-Finnish (FIN)

AF:

0.192

AC:

2029

AN:

10588

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18597

AN:

67940

Other (OTH)

AF:

0.291

AC:

615

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1561

3122

4684

6245

7806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.274

Hom.:

3560

Bravo

AF:

0.282

Asia WGS

AF:

0.264

AC:

919

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

(source)

DANN

Benign

0.79

PhyloP100

0.054

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over