rs8020095

chr14-66987141-G-A

Variant summary

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

The NM_020806.5(GPHN):c.963+21816G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,026 control chromosomes in the GnomAD database, including 13,664 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 0.35 (13664 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5	c.963+21816G>A		intron_variant		ENST00000478722.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6	c.963+21816G>A		intron_variant		1	NM_020806.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53415 AN: 151908 Hom.: 13617 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.352 AC: 53528 AN: 152026 Hom.: 13664 Cov.: 32 AF XY: 0.353 AC XY: 26211 AN XY: 74322

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.347

Alfa AF: 0.200 Hom.: 8139

Bravo AF: 0.386

Asia WGS AF: 0.409 AC: 1422 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	12
Dann	Benign	0.42

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: rs8020095; hg19: chr14-67453858;