rs17182817

chr14-66680045-A-G

Variant summary

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

The NM_020806.5(GPHN):c.65-1062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 152,332 control chromosomes in the GnomAD database, including 358 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 0.059 (358 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5	c.65-1062A>G		intron_variant		ENST00000478722.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6	c.65-1062A>G		intron_variant		1	NM_020806.5

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8928 AN: 152214 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0678

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

GnomAD4 genome AF: 0.0586 AC: 8926 AN: 152332 Hom.: 358 Cov.: 32 AF XY: 0.0569 AC XY: 4235 AN XY: 74480

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0818 Hom.: 513

Bravo AF: 0.0571

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	10
Dann	Benign	0.45

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: rs17182817; hg19: chr14-67146763;