dbSNP rs474122: DLGAP1:c.1592-20866T>C (chr18-3603114-A-G) – 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.1592-20866T>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.765

Publications

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

DLGAP1-AS2 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=-0.77).

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 rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4 link	c.1592-20866T>C		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.1592-20866T>C		intron_variant	Intron 7 of 12	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104573

AN:

151892

Hom.:

36622

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.778

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.786

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.700

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.688

AC:

104597

AN:

152010

Hom.:

36623

Cov.:

AF XY:

0.693

AC XY:

51510

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.562

AC:

23264

AN:

41404

American (AMR)

AF:

0.646

AC:

9869

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

2518

AN:

3472

East Asian (EAS)

AF:

0.724

AC:

3738

AN:

5164

South Asian (SAS)

AF:

0.731

AC:

3531

AN:

4828

European-Finnish (FIN)

AF:

0.822

AC:

8687

AN:

10566

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50529

AN:

67978

Other (OTH)

AF:

0.689

AC:

1456

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1631

3262

4894

6525

8156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.728

Hom.:

35059

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

(source)

DANN

Benign

0.67

PhyloP100

0.77

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over