chr17-7206676-A-G

Position:

• chr17-7206676-A-G

Variant summary

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

The NM_001321075.3(DLG4):​c.96+1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,884 control chromosomes in the GnomAD database, including 23,532 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 0.55 (23532 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.96+1498T>C		intron_variant		ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.96+1498T>C		intron_variant		2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.8	c.225+1498T>C		intron_variant				ENSP00000497806.3
DLG4	ENST00000648896.1	c.195+1399T>C		intron_variant				ENSP00000497546.1
DLG4	ENST00000647975.1	c.31-2424T>C		intron_variant				ENSP00000497912.1
DLG4	ENST00000648658.1	c.108+1498T>C		intron_variant				ENSP00000496903.1
DLG4	ENST00000648760.1	c.-85+1498T>C		intron_variant				ENSP00000497462.1
DLG4	ENST00000650301.1	c.24+255T>C		intron_variant				ENSP00000497662.1
DLG4	ENST00000491753.2	n.225+1498T>C		intron_variant		2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83092 AN: 151768 Hom.: 23515 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.547 AC: 83141 AN: 151884 Hom.: 23532 Cov.: 31 AF XY: 0.552 AC XY: 40974 AN XY: 74248

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.575

Alfa AF: 0.602 Hom.: 36136

Bravo AF: 0.524

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.80

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: rs390200; hg19: chr17-7109995;