4-67738448-T-TA

Position:

• chr4-67738448-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000406.3(GNRHR):​c.*2031_*2032insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000911 in 143,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.00091 (0 hom., cov: 32)
• Consequence: GNRHR NM_000406.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.33

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNRHR	NM_000406.3	c.*2031_*2032insT		3_prime_UTR_variant	3/3	ENST00000226413.5	NP_000397.1
GNRHR	NM_001012763.2	c.*2140_*2141insT		3_prime_UTR_variant	3/3		NP_001012781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNRHR	ENST00000226413.5	c.*2031_*2032insT		3_prime_UTR_variant	3/3	1	NM_000406.3	ENSP00000226413	P1
UBA6-DT	ENST00000500538.7	n.1920+6115dup		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000918 AC: 132 AN: 143774 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00240

Gnomad FIN AF: 0.000571

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.000508

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

GnomAD4 genome AF: 0.000911 AC: 131 AN: 143828 Hom.: 0 Cov.: 32 AF XY: 0.00100 AC XY: 70 AN XY: 69806

Gnomad4 AFR AF: 0.00175

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.000571

Gnomad4 NFE AF: 0.000414

Gnomad4 OTH AF: 0.000504

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Isolated GnRH Deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs766610755; hg19: chr4-68604166;