rs17247749

Variant names:

• chr14-66756365-A-G
• rs17247749
• NM_020806.5:c.144-20099A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-66756365-A-G
• chr14-66756365-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020806.5(GPHN):​c.144-20099A>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 151,880 control chromosomes in the GnomAD database, including 11,198 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 (11198 hom., cov: 31)
• Consequence: GPHN NM_020806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 7 publications found

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]

GPHN Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	NM_020806.5	c.144-20099A>G		intron_variant	Intron 2 of 22	ENST00000478722.6	NP_065857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHN	ENST00000478722.6	c.144-20099A>G		intron_variant	Intron 2 of 22	1	NM_020806.5	ENSP00000417901.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47222 AN: 151762 Hom.: 11182 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.121

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: 47291 AN: 151880 Hom.: 11198 Cov.: 31 AF XY: 0.314 AC XY: 23343 AN XY: 74254

African (AFR) AF: 0.637 AC: 26363 AN: 41390

American (AMR) AF: 0.372 AC: 5666 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3468

East Asian (EAS) AF: 0.462 AC: 2380 AN: 5148

South Asian (SAS) AF: 0.323 AC: 1550 AN: 4802

European-Finnish (FIN) AF: 0.144 AC: 1525 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8209 AN: 67952

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.239 Hom.: 1213

Bravo AF: 0.345

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.38
DANN	Benign	0.37
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17247749; hg19: chr14-67223083;