4-67738314-C-T

Variant names:

• chr4-67738314-C-T
• rs7666201
• NM_000406.3:c.*2166G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000406.3(GNRHR):​c.*2166G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,148 control chromosomes in the GnomAD database, including 11,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11593 hom., cov: 31)
• Consequence: GNRHR NM_000406.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 4-67738314-C-T is Benign according to our data. Variant chr4-67738314-C-T is described in ClinVar as Benign. ClinVar VariationId is 349423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000406.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRHR	NM_000406.3	MANE Select	c.*2166G>A		3_prime_UTR	Exon 3 of 3	NP_000397.1	P30968-1
	GNRHR	NM_001012763.2		c.*2275G>A		3_prime_UTR	Exon 3 of 3	NP_001012781.1	P30968-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRHR	ENST00000226413.5	TSL:1 MANE Select	c.*2166G>A		3_prime_UTR	Exon 3 of 3	ENSP00000226413.5	P30968-1
	UBA6-DT	ENST00000500538.7	TSL:1	n.1920+5969C>T		intron	N/A
	UBA6-DT	ENST00000502758.1	TSL:4	n.202+5969C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58823 AN: 151030 Hom.: 11573 Cov.: 31

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.390 AC: 58881 AN: 151148 Hom.: 11593 Cov.: 31 AF XY: 0.387 AC XY: 28595 AN XY: 73830

African (AFR) AF: 0.393 AC: 16227 AN: 41308

American (AMR) AF: 0.363 AC: 5504 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1469 AN: 3448

East Asian (EAS) AF: 0.322 AC: 1662 AN: 5162

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4812

European-Finnish (FIN) AF: 0.393 AC: 4085 AN: 10388

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 26869 AN: 67556

Other (OTH) AF: 0.382 AC: 802 AN: 2102

Alfa AF: 0.387 Hom.: 3992

Bravo AF: 0.392

Asia WGS AF: 0.305 AC: 1060 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypogonadotropic hypogonadism 7 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		0.046

Splicing

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

Other links and lift over

dbSNP: rs7666201; hg19: chr4-68604032;