Variant chr18-3581968-G-A details in Genebe, Genetics Data Aggregator

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

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]

DLGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

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

Synonymous conserved (PhyloP=-4.64 with no splicing effect.

BA1

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
DLGAP1	NM_004746.4 linkuse as main transcript	c.1872C>T	p.Thr624=	synonymous_variant	8/13	ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8 linkuse as main transcript	c.1872C>T	p.Thr624=	synonymous_variant	8/13	5	NM_004746.4	P1	O14490-1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29289

AN:

151962

Hom.:

3649

Cov.:

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.:

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

AF:

0.193

AC:

29280

AN:

152080

Hom.:

3647

Cov.:

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 submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This 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 submitter

clinical testing

GeneDx

Apr 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over