rs61746232

Variant names:

• chr18-3879181-C-T
• rs61746232
• NM_004746.4:c.888G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-3879181-C-T
• chr18-3879181-C-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.888G>A​(p.Ser296Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,526,094 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (30 hom.)
• Consequence: DLGAP1 NM_004746.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.34
• 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-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=-0.74).
• BP6: Variant 18-3879181-C-T is Benign according to our data. Variant chr18-3879181-C-T is described in ClinVar as Benign. ClinVar VariationId is 777265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1632/152302) while in subpopulation AFR AF = 0.0296 (1231/41566). AF 95% confidence interval is 0.0282. There are 21 homozygotes in GnomAd4. There are 792 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1632 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.888G>A	p.Ser296Ser	synonymous	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.888G>A	p.Ser296Ser	synonymous	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.888G>A	p.Ser296Ser	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.888G>A	p.Ser296Ser	synonymous	Exon 4 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000498188.5	TSL:1	n.896G>A		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+890C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1635 AN: 152184 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00527 AC: 965 AN: 183182 AF XY: 0.00487

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.00864

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000115

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.00734

GnomAD4 exome AF: 0.00238 AC: 3274 AN: 1373792 Hom.: 30 Cov.: 31 AF XY: 0.00250 AC XY: 1681 AN XY: 673712

African (AFR) AF: 0.0282 AC: 862 AN: 30592

American (AMR) AF: 0.00856 AC: 267 AN: 31178

Ashkenazi Jewish (ASJ) AF: 0.00895 AC: 182 AN: 20328

East Asian (EAS) AF: 0.00 AC: 0 AN: 38828

South Asian (SAS) AF: 0.00328 AC: 234 AN: 71432

European-Finnish (FIN) AF: 0.0000200 AC: 1 AN: 50056

Middle Eastern (MID) AF: 0.0214 AC: 114 AN: 5338

European-Non Finnish (NFE) AF: 0.00121 AC: 1292 AN: 1069520

Other (OTH) AF: 0.00570 AC: 322 AN: 56520

GnomAD4 genome AF: 0.0107 AC: 1632 AN: 152302 Hom.: 21 Cov.: 32 AF XY: 0.0106 AC XY: 792 AN XY: 74472

African (AFR) AF: 0.0296 AC: 1231 AN: 41566

American (AMR) AF: 0.0126 AC: 193 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00159 AC: 108 AN: 68030

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.00568 Hom.: 6

Bravo AF: 0.0121

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.89
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

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: rs61746232; hg19: chr18-3879181; COSMIC: COSV100234817; COSMIC: COSV100234817;