rs2038398

chr14-66919011-T-G

Variant summary

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

The NM_020806.5(GPHN):c.456+2942T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,080 control chromosomes in the GnomAD database, including 9,372 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 0.25 (9372 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5	c.456+2942T>G		intron_variant		ENST00000478722.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6	c.456+2942T>G		intron_variant		1	NM_020806.5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37552 AN: 151962 Hom.: 9355 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.247 AC: 37625 AN: 152080 Hom.: 9372 Cov.: 32 AF XY: 0.252 AC XY: 18730 AN XY: 74364

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.224

Alfa AF: 0.167 Hom.: 1133

Bravo AF: 0.283

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.9
Dann	Benign	0.55

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: rs2038398; hg19: chr14-67385728;