chr18-3612721-T-C

Variant names:

• chr18-3612721-T-C
• rs17725070
• NM_004746.4:c.1592-30473A>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.1592-30473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,332 control chromosomes in the GnomAD database, including 840 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 0.093 (840 hom., cov: 33)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.1592-30473A>G		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.1622-30473A>G		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.1622-30473A>G		intron	N/A	NP_001385455.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.1592-30473A>G		intron	N/A	ENSP00000316377.3
	DLGAP1	ENST00000400147.6	TSL:1	c.686-30473A>G		intron	N/A	ENSP00000383011.2
	DLGAP1	ENST00000400145.6	TSL:1	c.686-30473A>G		intron	N/A	ENSP00000383010.2

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14148 AN: 152214 Hom.: 842 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0309

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0929 AC: 14150 AN: 152332 Hom.: 840 Cov.: 33 AF XY: 0.0906 AC XY: 6752 AN XY: 74490

African (AFR) AF: 0.0278 AC: 1154 AN: 41580

American (AMR) AF: 0.0867 AC: 1326 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3468

East Asian (EAS) AF: 0.0479 AC: 249 AN: 5194

South Asian (SAS) AF: 0.177 AC: 857 AN: 4830

European-Finnish (FIN) AF: 0.0687 AC: 729 AN: 10618

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8970 AN: 68028

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.123 Hom.: 1964

Bravo AF: 0.0883

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.88
PhyloP100		0.58
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: rs17725070; hg19: chr18-3612720;