rs3759757

Positions:

• chr14-67611110-G-C

Variant summary

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

The XM_047430879.1(GPHN):​c.1313-124085G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 154,256 control chromosomes in the GnomAD database, including 18,079 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 (17956 hom., cov: 31)
  • Exomes 𝑓: 0.31 (123 hom.)
• Consequence: GPHN XM_047430879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

Genes affected

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ENSG00000259502 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1313-124085G>C		intron_variant			XP_047286835.1
LOC100419668		n.67611110G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000259502	ENST00000559594.1	n.125G>C		non_coding_transcript_exon_variant	1/3	6

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65181 AN: 151834 Hom.: 17900 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.306 AC: 704 AN: 2304 Hom.: 123 Cov.: 0 AF XY: 0.305 AC XY: 340 AN XY: 1114

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.430 AC: 65307 AN: 151952 Hom.: 17956 Cov.: 31 AF XY: 0.427 AC XY: 31680 AN XY: 74254

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.441

Alfa AF: 0.362 Hom.: 1624

Bravo AF: 0.457

Asia WGS AF: 0.428 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759757; hg19: chr14-68077827;