rs1952070

chr14-66641352-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.65-39755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,082 control chromosomes in the GnomAD database, including 11,184 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 0.31 (11184 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPHN	NM_020806.5	c.65-39755A>G		intron_variant		ENST00000478722.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPHN	ENST00000478722.6	c.65-39755A>G		intron_variant		1	NM_020806.5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47168 AN: 151964 Hom.: 11168 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.311 AC: 47237 AN: 152082 Hom.: 11184 Cov.: 32 AF XY: 0.313 AC XY: 23295 AN XY: 74346

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.294

Alfa AF: 0.175 Hom.: 1740

Bravo AF: 0.344

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.8
Dann	Benign	0.44

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: rs1952070; hg19: chr14-67108070;