rs8015408

Positions:

• chr14-66679962-C-G
• chr14-66679962-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.65-1145C>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 151,954 control chromosomes in the GnomAD database, including 11,175 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 (11175 hom., cov: 32)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.91).
• 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	Protein	UniProt
GPHN	NM_020806.5	c.65-1145C>G		intron_variant		ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.65-1145C>G		intron_variant		1	NM_020806.5	ENSP00000417901

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47206 AN: 151836 Hom.: 11159 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.311 AC: 47275 AN: 151954 Hom.: 11175 Cov.: 32 AF XY: 0.314 AC XY: 23320 AN XY: 74262

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.295

Alfa AF: 0.203 Hom.: 673

Bravo AF: 0.345

Asia WGS AF: 0.369 AC: 1282 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.69

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: rs8015408; hg19: chr14-67146680;