chr18-3814148-C-G

Variant names:

• chr18-3814148-C-G
• rs3786431
• NM_004746.4:c.1083G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004746.4(DLGAP1):​c.1083G>C​(p.Thr361Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,613,844 control chromosomes in the GnomAD database, including 4,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (1503 hom., cov: 31)
  • Exomes 𝑓: 0.044 (2758 hom.)
• Consequence: DLGAP1 NM_004746.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.190
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-3814148-C-G is Benign according to our data. Variant chr18-3814148-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060984.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.1083G>C	p.Thr361Thr	synonymous	Exon 5 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.1083G>C	p.Thr361Thr	synonymous	Exon 5 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.1083G>C	p.Thr361Thr	synonymous	Exon 5 of 14	NP_001385455.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.1083G>C	p.Thr361Thr	synonymous	Exon 5 of 13	ENSP00000316377.3
	DLGAP1	ENST00000400147.6	TSL:1	c.177G>C	p.Thr59Thr	synonymous	Exon 2 of 10	ENSP00000383011.2
	DLGAP1	ENST00000400145.6	TSL:1	c.177G>C	p.Thr59Thr	synonymous	Exon 2 of 9	ENSP00000383010.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15528 AN: 151860 Hom.: 1498 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0786

GnomAD2 exomes AF: 0.0672 AC: 16871 AN: 251036 AF XY: 0.0652

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.0689

Gnomad ASJ exome AF: 0.0770

Gnomad EAS exome AF: 0.0662

Gnomad FIN exome AF: 0.0507

Gnomad NFE exome AF: 0.0303

Gnomad OTH exome AF: 0.0583

GnomAD4 exome AF: 0.0445 AC: 65048 AN: 1461866 Hom.: 2758 Cov.: 32 AF XY: 0.0455 AC XY: 33068 AN XY: 727234

African (AFR) AF: 0.256 AC: 8559 AN: 33478

American (AMR) AF: 0.0694 AC: 3102 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 2101 AN: 26136

East Asian (EAS) AF: 0.0704 AC: 2793 AN: 39698

South Asian (SAS) AF: 0.104 AC: 8954 AN: 86258

European-Finnish (FIN) AF: 0.0497 AC: 2654 AN: 53420

Middle Eastern (MID) AF: 0.0364 AC: 210 AN: 5768

European-Non Finnish (NFE) AF: 0.0299 AC: 33236 AN: 1111990

Other (OTH) AF: 0.0569 AC: 3439 AN: 60394

GnomAD4 genome AF: 0.102 AC: 15561 AN: 151978 Hom.: 1503 Cov.: 31 AF XY: 0.102 AC XY: 7610 AN XY: 74298

African (AFR) AF: 0.253 AC: 10469 AN: 41408

American (AMR) AF: 0.0757 AC: 1155 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3466

East Asian (EAS) AF: 0.0619 AC: 319 AN: 5156

South Asian (SAS) AF: 0.107 AC: 517 AN: 4812

European-Finnish (FIN) AF: 0.0545 AC: 577 AN: 10584

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0296 AC: 2014 AN: 67972

Other (OTH) AF: 0.0773 AC: 163 AN: 2108

Alfa AF: 0.0279 Hom.: 49

Bravo AF: 0.110

Asia WGS AF: 0.103 AC: 361 AN: 3478

EpiCase AF: 0.0330

EpiControl AF: 0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DLGAP1-related disorder Benign:1

Jun 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		-0.19
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3786431; hg19: chr18-3814148; COSMIC: COSV59838507; COSMIC: COSV59838507;