rs9284410

Variant names:

• chr18-4192281-G-A
• rs9284410
• NM_004746.4:c.-266-40994C>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.-266-40994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,960 control chromosomes in the GnomAD database, including 7,842 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 0.32 (7842 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• 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]

LOC124904239 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-266-40994C>T		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.-266-40994C>T		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581550.5	n.130-40994C>T		intron_variant	Intron 1 of 4	1
DLGAP1	ENST00000581527.5	c.-266-40994C>T		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000577430.1	n.152-40994C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47975 AN: 151842 Hom.: 7818 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.316 AC: 48056 AN: 151960 Hom.: 7842 Cov.: 32 AF XY: 0.316 AC XY: 23458 AN XY: 74276

African (AFR) AF: 0.415 AC: 17178 AN: 41418

American (AMR) AF: 0.287 AC: 4383 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3466

East Asian (EAS) AF: 0.335 AC: 1729 AN: 5168

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2751 AN: 10568

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18439 AN: 67936

Other (OTH) AF: 0.305 AC: 643 AN: 2110

Alfa AF: 0.287 Hom.: 11046

Bravo AF: 0.324

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-0.77
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: rs9284410; hg19: chr18-4192281;