rs474122

Variant names:

• chr18-3603114-A-G
• rs474122
• NM_004746.4:c.1592-20866T>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.1592-20866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,034 control chromosomes in the GnomAD database, including 36,632 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 0.69 (36623 hom., cov: 31)
  • Exomes 𝑓: 0.83 (9 hom.)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765
• Publications: 8 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-AS2 (HGNC:28146): (DLGAP1 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.1592-20866T>C		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.1622-20866T>C		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.1622-20866T>C		intron	N/A	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.1592-20866T>C		intron	N/A	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000400147.6	TSL:1	c.686-20866T>C		intron	N/A	ENSP00000383011.2	O14490-2
	DLGAP1	ENST00000400145.6	TSL:1	c.686-20866T>C		intron	N/A	ENSP00000383010.2	O14490-3

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104573 AN: 151892 Hom.: 36622 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.833 AC: 20 AN: 24 Hom.: 9 Cov.: 0 AF XY: 0.778 AC XY: 14 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.786 AC: 11 AN: 14

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.688 AC: 104597 AN: 152010 Hom.: 36623 Cov.: 31 AF XY: 0.693 AC XY: 51510 AN XY: 74290

African (AFR) AF: 0.562 AC: 23264 AN: 41404

American (AMR) AF: 0.646 AC: 9869 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2518 AN: 3472

East Asian (EAS) AF: 0.724 AC: 3738 AN: 5164

South Asian (SAS) AF: 0.731 AC: 3531 AN: 4828

European-Finnish (FIN) AF: 0.822 AC: 8687 AN: 10566

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50529 AN: 67978

Other (OTH) AF: 0.689 AC: 1456 AN: 2114

Alfa AF: 0.728 Hom.: 35059

Bravo AF: 0.665

Asia WGS AF: 0.731 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.67
PhyloP100		0.77
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: rs474122; hg19: chr18-3603112;