rs12885261

Positions:

• chr14-67604853-C-T

Variant summary

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

The XM_047430879.1(GPHN):​c.1313-130342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,858 control chromosomes in the GnomAD database, including 15,993 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 0.45 (15993 hom., cov: 31)
• Consequence: GPHN XM_047430879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1313-130342C>T		intron_variant			XP_047286835.1
		n.67604853C>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68924 AN: 151740 Hom.: 15965 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.454 AC: 69007 AN: 151858 Hom.: 15993 Cov.: 31 AF XY: 0.457 AC XY: 33903 AN XY: 74212

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.452

Alfa AF: 0.430 Hom.: 8143

Bravo AF: 0.473

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12885261; hg19: chr14-68071570;