rs9646461

Variant names:

• chr18-4085990-G-A
• rs9646461
• NM_004746.4:c.-159+65190C>T

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+65190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,040 control chromosomes in the GnomAD database, including 6,483 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 0.28 (6483 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 0 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-159+65190C>T		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+65190C>T		intron_variant	Intron 2 of 12	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43080 AN: 151922 Hom.: 6481 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.283 AC: 43102 AN: 152040 Hom.: 6483 Cov.: 32 AF XY: 0.274 AC XY: 20378 AN XY: 74324

African (AFR) AF: 0.327 AC: 13538 AN: 41452

American (AMR) AF: 0.215 AC: 3280 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5174

South Asian (SAS) AF: 0.182 AC: 878 AN: 4820

European-Finnish (FIN) AF: 0.224 AC: 2365 AN: 10566

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21055 AN: 67982

Other (OTH) AF: 0.292 AC: 614 AN: 2104

Alfa AF: 0.297 Hom.: 11658

Bravo AF: 0.286

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		0.64
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: rs9646461; hg19: chr18-4085990;