rs6828922

chr4-67752733-T-Cchr4-67752733-T-G

Variant summary

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

The NM_000406.3(GNRHR):c.522+1081A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,094 control chromosomes in the GnomAD database, including 49,108 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 0.77 (49108 hom., cov: 32)
• Consequence: GNRHR NM_000406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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:49083): (UBA6 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNRHR	NM_000406.3	c.522+1081A>G		intron_variant		ENST00000226413.5
GNRHR	NM_001012763.2	c.522+1081A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNRHR	ENST00000226413.5	c.522+1081A>G		intron_variant		1	NM_000406.3	P1
UBA6-DT	ENST00000500538.7	n.1921-2456T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117090 AN: 151974 Hom.: 49109 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.770 AC: 117108 AN: 152094 Hom.: 49108 Cov.: 32 AF XY: 0.779 AC XY: 57931 AN XY: 74358

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.798

Alfa AF: 0.891 Hom.: 130261

Bravo AF: 0.742

Asia WGS AF: 0.913 AC: 3169 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.3
Dann	Benign	0.67

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: rs6828922; hg19: chr4-68618451;