18-4132821-C-T

Variant names:

• chr18-4132821-C-T
• rs976469
• NM_004746.4:c.-159+18359G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004746.4(DLGAP1):​c.-159+18359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,094 control chromosomes in the GnomAD database, including 313 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 0.039 (313 hom., cov: 33)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-159+18359G>A		intron_variant	Intron 2 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-159+18359G>A		intron_variant	Intron 2 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5850 AN: 151976 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.0297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0387 AC: 5887 AN: 152094 Hom.: 313 Cov.: 33 AF XY: 0.0376 AC XY: 2799 AN XY: 74356

African (AFR) AF: 0.121 AC: 4998 AN: 41472

American (AMR) AF: 0.0154 AC: 235 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4822

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10572

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 67982

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

Alfa AF: 0.00958 Hom.: 5

Bravo AF: 0.0420

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.93
DANN	Benign	0.51
PhyloP100		-0.38
Mutation Taster		=100/0	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: rs976469; hg19: chr18-4132821;