chr17-7188331-T-C

Variant names:

• chr17-7188331-T-C
• rs314253
• NM_001321075.3:c.*2377A>G

Variant summary

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

The NM_001321075.3(DLG4):​c.*2377A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,036 control chromosomes in the GnomAD database, including 10,494 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 0.37 (10494 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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 (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.*2377A>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506	c.*2377A>G		3_prime_UTR_variant	Exon 20 of 20	2	NM_001321075.3	ENSP00000382425.2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55886 AN: 151918 Hom.: 10478 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.368 AC: 55956 AN: 152036 Hom.: 10494 Cov.: 31 AF XY: 0.373 AC XY: 27729 AN XY: 74322

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.333

Alfa AF: 0.343 Hom.: 21039

Bravo AF: 0.374

Asia WGS AF: 0.356 AC: 1240 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	0.44
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs314253; hg19: chr17-7091650;