rs17248895

Variant names:

• chr14-67416907-A-C
• rs17248895
• ENST00000751530.1:n.225-3846T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-67416907-A-C
• chr14-67416907-A-T

Variant summary

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

The ENST00000751530.1(ENSG00000297881):​n.225-3846T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,204 control chromosomes in the GnomAD database, including 11,522 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 (11522 hom., cov: 33)
• Consequence: ENSG00000297881 ENST00000751530.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83
• Publications: 9 publications found

Genes affected

ENSG00000297881 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1313-318288A>C		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000297881	ENST00000751530.1	n.225-3846T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46745 AN: 152086 Hom.: 11489 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.308 AC: 46840 AN: 152204 Hom.: 11522 Cov.: 33 AF XY: 0.313 AC XY: 23292 AN XY: 74426

African (AFR) AF: 0.652 AC: 27062 AN: 41498

American (AMR) AF: 0.359 AC: 5493 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2423 AN: 5178

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4832

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10606

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

European-Non Finnish (NFE) AF: 0.108 AC: 7369 AN: 68016

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.176 Hom.: 5725

Bravo AF: 0.341

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.65
PhyloP100		-3.8

Splicing

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

Other links and lift over

dbSNP: rs17248895; hg19: chr14-67883624;