18-4437562-A-G

Variant names:

• chr18-4437562-A-G
• rs3913842
• NM_004746.4:c.-267+17444T>C

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+17444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 137,612 control chromosomes in the GnomAD database, including 20,939 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 0.57 (20939 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-267+17444T>C		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+17444T>C		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-267+17444T>C		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000579652.1	n.18-6480T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.572 AC: 78601 AN: 137518 Hom.: 20919 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.572 AC: 78646 AN: 137612 Hom.: 20939 Cov.: 32 AF XY: 0.574 AC XY: 38633 AN XY: 67320

African (AFR) AF: 0.445 AC: 16532 AN: 37128

American (AMR) AF: 0.606 AC: 8190 AN: 13522

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2148 AN: 3124

East Asian (EAS) AF: 0.685 AC: 3411 AN: 4980

South Asian (SAS) AF: 0.715 AC: 3206 AN: 4482

European-Finnish (FIN) AF: 0.581 AC: 5920 AN: 10186

Middle Eastern (MID) AF: 0.644 AC: 161 AN: 250

European-Non Finnish (NFE) AF: 0.613 AC: 37535 AN: 61242

Other (OTH) AF: 0.596 AC: 1120 AN: 1878

Alfa AF: 0.514 Hom.: 1826

Bravo AF: 0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.88
PhyloP100		0.67
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: rs3913842; hg19: chr18-4437562;