rs145691437

Variant names:

• chr18-3879217-G-T
• rs145691437
• NM_004746.4:c.852C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-3879217-G-T
• chr18-3879217-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004746.4(DLGAP1):​c.852C>A​(p.Thr284Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,574,608 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (77 hom.)
• Consequence: DLGAP1 NM_004746.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.07
• Publications: 4 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-AS3 (HGNC:27317): (DLGAP1 antisense RNA 3)

LOC124904238 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 18-3879217-G-T is Benign according to our data. Variant chr18-3879217-G-T is described in ClinVar as Benign. ClinVar VariationId is 771503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00397 (604/152314) while in subpopulation AMR AF = 0.0333 (509/15296). AF 95% confidence interval is 0.0309. There are 19 homozygotes in GnomAd4. There are 321 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 604 AD gene.

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.852C>A	p.Thr284Thr	synonymous	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.852C>A	p.Thr284Thr	synonymous	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.852C>A	p.Thr284Thr	synonymous	Exon 4 of 14	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.852C>A	p.Thr284Thr	synonymous	Exon 4 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000498188.5	TSL:1	n.860C>A		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+926G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152196 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00816 AC: 1813 AN: 222216 AF XY: 0.00643

Gnomad AFR exome AF: 0.000754

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000392

Gnomad OTH exome AF: 0.00680

GnomAD4 exome AF: 0.00172 AC: 2442 AN: 1422294 Hom.: 77 Cov.: 31 AF XY: 0.00151 AC XY: 1064 AN XY: 703306

African (AFR) AF: 0.000404 AC: 13 AN: 32176

American (AMR) AF: 0.0487 AC: 1911 AN: 39202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23632

East Asian (EAS) AF: 0.00660 AC: 259 AN: 39242

South Asian (SAS) AF: 0.000990 AC: 79 AN: 79830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52152

Middle Eastern (MID) AF: 0.000359 AC: 2 AN: 5564

European-Non Finnish (NFE) AF: 0.0000321 AC: 35 AN: 1091934

Other (OTH) AF: 0.00244 AC: 143 AN: 58562

GnomAD4 genome AF: 0.00397 AC: 604 AN: 152314 Hom.: 19 Cov.: 32 AF XY: 0.00431 AC XY: 321 AN XY: 74490

African (AFR) AF: 0.000625 AC: 26 AN: 41586

American (AMR) AF: 0.0333 AC: 509 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00735 AC: 38 AN: 5170

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.000365 Hom.: 0

Bravo AF: 0.00777

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DLGAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.11
DANN	Benign	0.85
PhyloP100		-2.1
Mutation Taster		=94/6	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: rs145691437; hg19: chr18-3879217; COSMIC: COSV107325438; COSMIC: COSV107325438;