rs10483790

Positions:

• chr14-66831452-C-T

Variant summary

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

The NM_020806.5(GPHN):​c.294+6886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 152,202 control chromosomes in the GnomAD database, including 187 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 0.043 (187 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPHN	NM_020806.5	c.294+6886C>T		intron_variant		ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.294+6886C>T		intron_variant		1	NM_020806.5	ENSP00000417901

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6603 AN: 152084 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0434 AC: 6603 AN: 152202 Hom.: 187 Cov.: 32 AF XY: 0.0420 AC XY: 3124 AN XY: 74420

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0400

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.00793

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0579 Hom.: 118

Bravo AF: 0.0407

Asia WGS AF: 0.0180 AC: 63 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54
DANN	Benign	0.32

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: rs10483790; hg19: chr14-67298170;