rs17574271

chr18-3970124-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+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

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=-0.68).
• 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/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.-73+34992A>G		intron_variant		ENST00000315677.8
DLGAP1-AS4	NR_102696.1	n.78+7694T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.-73+34992A>G		intron_variant		5	NM_004746.4	P1
DLGAP1-AS4	ENST00000652891.1	n.78+7694T>C		intron_variant, non_coding_transcript_variant
DLGAP1	ENST00000581527.5	c.-73+34992A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0662 Hom.: 325

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

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: rs17574271; hg19: chr18-3970124;