rs3822196

Positions:

• chr4-67749081-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000406.3(GNRHR):​c.523-4294T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,106 control chromosomes in the GnomAD database, including 4,169 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 0.23 (4169 hom., cov: 33)
• Consequence: GNRHR NM_000406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697

Genes affected

GNRHR (HGNC:4421): (gonadotropin releasing hormone receptor) This gene encodes the receptor for type 1 gonadotropin-releasing hormone. This receptor is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate. Following binding of gonadotropin-releasing hormone, the receptor associates with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Activation of the receptor ultimately causes the release of gonadotropic luteinizing hormone (LH) and follicle stimulating hormone (FSH). Defects in this gene are a cause of hypogonadotropic hypogonadism (HH). Alternative splicing results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for this gene. [provided by RefSeq, Jul 2008]

UBA6-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNRHR	NM_000406.3	c.523-4294T>C		intron_variant		ENST00000226413.5	NP_000397.1
GNRHR	NM_001012763.2	c.523-4422T>C		intron_variant			NP_001012781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNRHR	ENST00000226413.5	c.523-4294T>C		intron_variant		1	NM_000406.3	ENSP00000226413.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34327 AN: 151988 Hom.: 4167 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.226 AC: 34330 AN: 152106 Hom.: 4169 Cov.: 33 AF XY: 0.222 AC XY: 16508 AN XY: 74358

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.217

Alfa AF: 0.244 Hom.: 2385

Bravo AF: 0.227

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.90

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: rs3822196; hg19: chr4-68614799;