18-4389879-A-G

Variant names:

• chr18-4389879-A-G
• rs556831
• NM_004746.4:c.-267+65127T>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+65127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,156 control chromosomes in the GnomAD database, including 58,292 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 0.86 (58292 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-267+65127T>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+65127T>C		intron_variant	Intron 1 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-267+65127T>C		intron_variant	Intron 1 of 11	2		ENSP00000463864.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131528 AN: 152038 Hom.: 58265 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.865 AC: 131604 AN: 152156 Hom.: 58292 Cov.: 32 AF XY: 0.871 AC XY: 64766 AN XY: 74396

African (AFR) AF: 0.648 AC: 26861 AN: 41440

American (AMR) AF: 0.948 AC: 14482 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3372 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.964 AC: 4653 AN: 4826

European-Finnish (FIN) AF: 0.966 AC: 10245 AN: 10610

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63725 AN: 68020

Other (OTH) AF: 0.906 AC: 1918 AN: 2116

Alfa AF: 0.822 Hom.: 21604

Bravo AF: 0.855

Asia WGS AF: 0.960 AC: 3336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		1.4
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

Publications

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Other links and lift over

dbSNP: rs556831; hg19: chr18-4389879;