rs7144243

Variant names:

• chr14-67607715-A-G
• rs7144243
• XM_047430879.1:c.1313-127480A>G

Variant summary

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

The XM_047430879.1(GPHN):​c.1313-127480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,090 control chromosomes in the GnomAD database, including 3,327 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 0.21 (3327 hom., cov: 32)
• Consequence: GPHN XM_047430879.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHN	XM_047430879.1	c.1313-127480A>G		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31303 AN: 151972 Hom.: 3324 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.206 AC: 31326 AN: 152090 Hom.: 3327 Cov.: 32 AF XY: 0.207 AC XY: 15387 AN XY: 74350

African (AFR) AF: 0.203 AC: 8418 AN: 41478

American (AMR) AF: 0.183 AC: 2795 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 887 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5176

South Asian (SAS) AF: 0.205 AC: 989 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10562

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14172 AN: 67976

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.212 Hom.: 5708

Bravo AF: 0.199

Asia WGS AF: 0.183 AC: 636 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	5.3
DANN	Benign	0.84
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs7144243; hg19: chr14-68074432;