17-7197973-C-T

Position:

• chr17-7197973-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321075.3(DLG4):​c.788-921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,924 control chromosomes in the GnomAD database, including 14,349 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 0.43 (14349 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG4	NM_001321075.3	c.788-921G>A		intron_variant		ENST00000399506.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG4	ENST00000399506.9	c.788-921G>A		intron_variant		2	NM_001321075.3	A1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65186 AN: 151806 Hom.: 14331 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.429 AC: 65235 AN: 151924 Hom.: 14349 Cov.: 31 AF XY: 0.431 AC XY: 31968 AN XY: 74236

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.443

Alfa AF: 0.460 Hom.: 24671

Bravo AF: 0.415

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.66

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: rs3826408; hg19: chr17-7101292;