Variant 18-3879217-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004746.4(DLGAP1):c.852C>A(p.Thr284Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,574,608 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 77 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.07

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 (HGNC:):

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=-0.55).

BP6

Variant 18-3879217-G-T is Benign according to our data. Variant chr18-3879217-G-T is described in ClinVar as [Benign]. Clinvar id is 771503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00397 (604/152314) while in subpopulation AMR AF= 0.0333 (509/15296). AF 95% confidence interval is 0.0309. There are 19 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 604 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4 linkuse as main transcript	c.852C>A	p.Thr284Thr	synonymous_variant	4/13	ENST00000315677.8	NP_004737.2	O14490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8 linkuse as main transcript	c.852C>A	p.Thr284Thr	synonymous_variant	4/13	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

596

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00733

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00816

AC:

1813

AN:

222216

Hom.:

AF XY:

0.00643

AC XY:

767

AN XY:

119318

show subpopulations

Gnomad AFR exome

AF:

0.000754

Gnomad AMR exome

AF:

0.0511

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0126

Gnomad SAS exome

AF:

0.000704

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00680

GnomAD4 exome

AF:

0.00172

AC:

2442

AN:

1422294

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1064

AN XY:

703306

show subpopulations

Gnomad4 AFR exome

AF:

0.000404

Gnomad4 AMR exome

AF:

0.0487

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00660

Gnomad4 SAS exome

AF:

0.000990

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00397

AC:

604

AN:

152314

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.0333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00735

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.000365

Hom.:

Bravo

AF:

0.00777

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -

DLGAP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.11

DANN

Benign

0.85

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