rs1290900

Positions:

• chr14-67234451-C-A

Variant summary

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

The XM_047430879.1(GPHN):​c.1312+175665C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,042 control chromosomes in the GnomAD database, including 20,449 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 0.47 (20449 hom., cov: 31)
• Consequence: GPHN XM_047430879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1312+175665C>A		intron_variant			XP_047286835.1
		n.67234451C>A		intergenic_region
LOC124903330	XR_007064217.1	n.2121-3324G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71873 AN: 151924 Hom.: 20460 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.473 AC: 71851 AN: 152042 Hom.: 20449 Cov.: 31 AF XY: 0.476 AC XY: 35332 AN XY: 74298

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.497

Alfa AF: 0.601 Hom.: 49126

Bravo AF: 0.445

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1290900; hg19: chr14-67701168;