rs17574271

Variant names:

• chr18-3970124-T-C
• rs17574271
• NM_004746.4:c.-73+34992A>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.-73+34992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,276 control chromosomes in the GnomAD database, including 246 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 0.048 (246 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875
• Publications: 2 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.-73+34992A>G		intron_variant	Intron 3 of 12	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-73+34992A>G		intron_variant	Intron 3 of 12	5	NM_004746.4	ENSP00000316377.3
DLGAP1	ENST00000581527.5	c.-73+34992A>G		intron_variant	Intron 3 of 11	2		ENSP00000463864.1
DLGAP1-AS4	ENST00000652891.1	n.78+7694T>C		intron_variant	Intron 1 of 4
DLGAP1-AS4	ENST00000767594.1	n.312-22967T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7269 AN: 152158 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0477 AC: 7271 AN: 152276 Hom.: 246 Cov.: 32 AF XY: 0.0456 AC XY: 3393 AN XY: 74468

African (AFR) AF: 0.0143 AC: 595 AN: 41558

American (AMR) AF: 0.0307 AC: 469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0644 AC: 311 AN: 4832

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0751 AC: 5106 AN: 68006

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0588 Hom.: 431

Bravo AF: 0.0452

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.88
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: rs17574271; hg19: chr18-3970124;