8-25423105-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001083111.2(GNRH1):c.141+85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,011,756 control chromosomes in the GnomAD database, including 1,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (747 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (438 hom.)
• Consequence: GNRH1 NM_001083111.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

Genes affected

GNRH1 (HGNC:4419): (gonadotropin releasing hormone 1) This gene encodes a preproprotein that is proteolytically processed to generate a peptide that is a member of the gonadotropin-releasing hormone (GnRH) family of peptides. Alternative splicing results in multiple transcript variants, at least one of which is secreted and then cleaved to generate gonadoliberin-1 and GnRH-associated peptide 1. Gonadoliberin-1 stimulates the release of luteinizing and follicle stimulating hormones, which are important for reproduction. Mutations in this gene are associated with hypogonadotropic hypogonadism. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-25423105-T-C is Benign according to our data. Variant chr8-25423105-T-C is described in ClinVar as [Benign]. Clinvar id is 1255191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNRH1	NM_001083111.2	c.141+85A>G		intron_variant		ENST00000421054.7
GNRH1	NM_000825.3	c.153+85A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNRH1	ENST00000421054.7	c.141+85A>G		intron_variant		1	NM_001083111.2	P1
GNRH1	ENST00000276414.4	c.141+85A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8163 AN: 152180 Hom.: 746 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.00613 AC: 5267 AN: 859458 Hom.: 438 AF XY: 0.00492 AC XY: 2230 AN XY: 452868

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.00963

Gnomad4 ASJ exome AF: 0.000179

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.000486

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome AF: 0.0537 AC: 8185 AN: 152298 Hom.: 747 Cov.: 32 AF XY: 0.0517 AC XY: 3851 AN XY: 74464

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0435 Hom.: 78

Bravo AF: 0.0620

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.99
Dann	Benign	0.52

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: rs17053646; hg19: chr8-25280621;