18-4453498-T-C

Variant names:

• chr18-4453498-T-C
• rs9951521
• NM_004746.4:c.-267+1508A>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.-267+1508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,958 control chromosomes in the GnomAD database, including 31,592 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 0.64 (31592 hom., cov: 31)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-267+1508A>G		intron_variant	Intron 1 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-267+1508A>G		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-267+1508A>G		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000579652.1	n.17+1508A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97769 AN: 151840 Hom.: 31555 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.644 AC: 97858 AN: 151958 Hom.: 31592 Cov.: 31 AF XY: 0.645 AC XY: 47921 AN XY: 74262

African (AFR) AF: 0.669 AC: 27723 AN: 41450

American (AMR) AF: 0.647 AC: 9890 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1962 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3240 AN: 5140

South Asian (SAS) AF: 0.581 AC: 2800 AN: 4816

European-Finnish (FIN) AF: 0.717 AC: 7557 AN: 10538

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42530 AN: 67942

Other (OTH) AF: 0.607 AC: 1280 AN: 2108

Alfa AF: 0.642 Hom.: 6704

Bravo AF: 0.639

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		-0.12
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: rs9951521; hg19: chr18-4453498;