rs16946196

Variant names:

• chr18-4191055-C-A
• rs16946196
• NM_004746.4:c.-266-39768G>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.-266-39768G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,088 control chromosomes in the GnomAD database, including 863 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 (863 hom., cov: 33)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-266-39768G>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.-266-39768G>T		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581550.5	n.130-39768G>T		intron_variant	Intron 1 of 4	1
DLGAP1	ENST00000581527.5	c.-266-39768G>T		intron_variant	Intron 1 of 11	2		ENSP00000463864.1
DLGAP1	ENST00000577430.1	n.152-39768G>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14135 AN: 151970 Hom.: 862 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.0930 AC: 14139 AN: 152088 Hom.: 863 Cov.: 33 AF XY: 0.0941 AC XY: 6995 AN XY: 74350

African (AFR) AF: 0.0407 AC: 1690 AN: 41524

American (AMR) AF: 0.136 AC: 2070 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1421 AN: 5152

South Asian (SAS) AF: 0.0722 AC: 348 AN: 4822

European-Finnish (FIN) AF: 0.0913 AC: 965 AN: 10570

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7112 AN: 67976

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0954 Hom.: 145

Bravo AF: 0.0958

Asia WGS AF: 0.156 AC: 541 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.62
PhyloP100		-1.1
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: rs16946196; hg19: chr18-4191055;