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GeneBe

18-3581968-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004746.4(DLGAP1):c.1872C>T(p.Thr624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,932 control chromosomes in the GnomAD database, including 51,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3647 hom., cov: 31)
Exomes 𝑓: 0.25 ( 48153 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.64
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-3581968-G-A is Benign according to our data. Variant chr18-3581968-G-A is described in ClinVar as [Benign]. Clinvar id is 1292003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.64 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLGAP1NM_004746.4 linkuse as main transcriptc.1872C>T p.Thr624= synonymous_variant 8/13 ENST00000315677.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLGAP1ENST00000315677.8 linkuse as main transcriptc.1872C>T p.Thr624= synonymous_variant 8/135 NM_004746.4 P1O14490-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.193
AC:
29289
AN:
151962
Hom.:
3649
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0598
Gnomad AMI
AF:
0.365
Gnomad AMR
AF:
0.221
Gnomad ASJ
AF:
0.229
Gnomad EAS
AF:
0.00444
Gnomad SAS
AF:
0.136
Gnomad FIN
AF:
0.282
Gnomad MID
AF:
0.266
Gnomad NFE
AF:
0.267
Gnomad OTH
AF:
0.192
GnomAD3 exomes
AF:
0.210
AC:
52366
AN:
249834
Hom.:
6533
AF XY:
0.215
AC XY:
29057
AN XY:
135178
show subpopulations
Gnomad AFR exome
AF:
0.0563
Gnomad AMR exome
AF:
0.190
Gnomad ASJ exome
AF:
0.223
Gnomad EAS exome
AF:
0.00201
Gnomad SAS exome
AF:
0.146
Gnomad FIN exome
AF:
0.273
Gnomad NFE exome
AF:
0.274
Gnomad OTH exome
AF:
0.239
GnomAD4 exome
AF:
0.248
AC:
362910
AN:
1461852
Hom.:
48153
Cov.:
37
AF XY:
0.247
AC XY:
179524
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0519
Gnomad4 AMR exome
AF:
0.192
Gnomad4 ASJ exome
AF:
0.217
Gnomad4 EAS exome
AF:
0.00171
Gnomad4 SAS exome
AF:
0.148
Gnomad4 FIN exome
AF:
0.270
Gnomad4 NFE exome
AF:
0.274
Gnomad4 OTH exome
AF:
0.228
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.193
AC:
29280
AN:
152080
Hom.:
3647
Cov.:
31
AF XY:
0.193
AC XY:
14328
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0595
Gnomad4 AMR
AF:
0.221
Gnomad4 ASJ
AF:
0.229
Gnomad4 EAS
AF:
0.00445
Gnomad4 SAS
AF:
0.137
Gnomad4 FIN
AF:
0.282
Gnomad4 NFE
AF:
0.267
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.243
Hom.:
7696
Bravo
AF:
0.181
Asia WGS
AF:
0.0720
AC:
255
AN:
3478
EpiCase
AF:
0.268
EpiControl
AF:
0.278

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

DLGAP1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxApr 23, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
1.2
Dann
Benign
0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56017170; hg19: chr18-3581966; COSMIC: COSV59808973; COSMIC: COSV59808973; API