chr18-3993987-T-C

Position:

• chr18-3993987-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004746.4(DLGAP1):​c.-73+11129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,020 control chromosomes in the GnomAD database, including 5,870 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 0.27 (5870 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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]

DLGAP1-AS4 (HGNC:44333): (DLGAP1 antisense RNA 4)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-73+11129A>G		intron_variant		ENST00000315677.8	NP_004737.2
DLGAP1-AS4	NR_102696.1	n.190+785T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-73+11129A>G		intron_variant		5	NM_004746.4	ENSP00000316377	P1
DLGAP1-AS4	ENST00000652891.1	n.190+785T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41746 AN: 151902 Hom.: 5864 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.275 AC: 41770 AN: 152020 Hom.: 5870 Cov.: 32 AF XY: 0.274 AC XY: 20405 AN XY: 74336

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.291

Alfa AF: 0.274 Hom.: 3238

Bravo AF: 0.282

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs988920; hg19: chr18-3993987;