Genetic Variant DLG4:c.210+40G>A (chr17-7203968-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321075.3(DLG4):c.210+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,603,206 control chromosomes in the GnomAD database, including 274 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 0.022 ( 143 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 131 hom. )

Consequence

DLG4
NM_001321075.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Variant links:

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLG4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3 link	c.210+40G>A		intron_variant	Intron 4 of 19	ENST00000399506.9	NP_001308004.1	P78352-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG4	ENST00000399506.9 link	c.210+40G>A	intron_variant	Intron 4 of 19	2	NM_001321075.3	ENSP00000382425.2	P78352-1
DLG4	ENST00000648172.8 link	c.339+40G>A	intron_variant	Intron 6 of 21			ENSP00000497806.3	P78352-2
DLG4	ENST00000648896.1 link	c.309+40G>A	intron_variant	Intron 4 of 19			ENSP00000497546.1	A0A3B3ISQ5
DLG4	ENST00000649520.1 link	c.30+40G>A	intron_variant	Intron 3 of 18			ENSP00000497647.1	B7Z647
DLG4	ENST00000648263.1 link	c.30+40G>A	intron_variant	Intron 2 of 13			ENSP00000498035.1	A0A3B3IU19
DLG4	ENST00000647975.1 link	c.144+40G>A	intron_variant	Intron 3 of 6			ENSP00000497912.1	A0A3B3ITI9
DLG4	ENST00000451807.7 link	c.126+40G>A	intron_variant	Intron 3 of 7	5		ENSP00000407918.3	C9JYG3
DLG4	ENST00000648658.1 link	c.222+40G>A	intron_variant	Intron 4 of 5			ENSP00000496903.1	A0A3B3IRP2
DLG4	ENST00000648760.1 link	c.30+40G>A	intron_variant	Intron 3 of 3			ENSP00000497462.1	A0A3B3ISL1
DLG4	ENST00000650301.1 link	c.138+40G>A	intron_variant	Intron 3 of 3			ENSP00000497662.1	A0A3B3ITD1
DLG4	ENST00000491753.2 link	n.339+40G>A	intron_variant	Intron 6 of 20	2		ENSP00000467897.2	B7Z3U2

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3351

AN:

152068

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00943

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00594

AC:

1378

AN:

232128

Hom.:

AF XY:

0.00461

AC XY:

579

AN XY:

125698

show subpopulations

Gnomad AFR exome

AF:

0.0841

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000382

Gnomad OTH exome

AF:

0.00316

GnomAD4 exome

AF:

0.00254

AC:

3681

AN:

1451020

Hom.:

131

Cov.:

AF XY:

0.00219

AC XY:

1576

AN XY:

720942

show subpopulations

Gnomad4 AFR exome

AF:

0.0855

Gnomad4 AMR exome

AF:

0.00552

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.0220

AC:

3354

AN:

152186

Hom.:

143

Cov.:

AF XY:

0.0211

AC XY:

1567

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0763

Gnomad4 AMR

AF:

0.00942

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.50

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over