chr18-4133739-T-C

Variant names:

• chr18-4133739-T-C
• rs1402627
• NM_004746.4:c.-159+17441A>G

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+17441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,166 control chromosomes in the GnomAD database, including 56,007 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 0.85 (56007 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-159+17441A>G		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+17441A>G		intron_variant	Intron 2 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129880 AN: 152048 Hom.: 55946 Cov.: 32

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.854 AC: 130001 AN: 152166 Hom.: 56007 Cov.: 32 AF XY: 0.857 AC XY: 63757 AN XY: 74390

African (AFR) AF: 0.962 AC: 39940 AN: 41536

American (AMR) AF: 0.847 AC: 12926 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2944 AN: 3470

East Asian (EAS) AF: 0.824 AC: 4254 AN: 5162

South Asian (SAS) AF: 0.956 AC: 4612 AN: 4824

European-Finnish (FIN) AF: 0.832 AC: 8822 AN: 10598

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53821 AN: 67998

Other (OTH) AF: 0.834 AC: 1764 AN: 2114

Alfa AF: 0.817 Hom.: 96878

Bravo AF: 0.859

Asia WGS AF: 0.889 AC: 3093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.58
PhyloP100		-3.5
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: rs1402627; hg19: chr18-4133739;