Variant chr8-25423150-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083111.2(GNRH1):c.141+40T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,413,348 control chromosomes in the GnomAD database, including 693,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70517 hom., cov: 32)

Exomes 𝑓: 0.99 ( 623278 hom. )

Consequence

GNRH1
NM_001083111.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.276

Variant links:

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]

GNRH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-25423150-A-C is Benign according to our data. Variant chr8-25423150-A-C is described in ClinVar as [Benign]. Clinvar id is 1230178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNRH1	NM_001083111.2 link	c.141+40T>G		intron_variant		ENST00000421054.7	NP_001076580.1	P01148
GNRH1	NM_000825.3 link	c.153+40T>G		intron_variant			NP_000816.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNRH1	ENST00000421054.7 link	c.141+40T>G		intron_variant		1	NM_001083111.2	ENSP00000391280.2		P01148
GNRH1	ENST00000276414.4 link	c.141+40T>G		intron_variant		1		ENSP00000276414.4		P01148

Frequencies

GnomAD3 genomes

AF:

0.961

AC:

146192

AN:

152100

Hom.:

70477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

0.970

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.985

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.974

GnomAD3 exomes

AF:

0.987

AC:

245390

AN:

248526

Hom.:

121255

AF XY:

0.989

AC XY:

133483

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.988

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.994

AC:

1253542

AN:

1261130

Hom.:

623278

Cov.:

AF XY:

0.994

AC XY:

634437

AN XY:

638130

show subpopulations

Gnomad4 AFR exome

AF:

0.869

Gnomad4 AMR exome

AF:

0.992

Gnomad4 ASJ exome

AF:

0.969

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.989

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.987

GnomAD4 genome

AF:

0.961

AC:

146289

AN:

152218

Hom.:

70517

Cov.:

AF XY:

0.962

AC XY:

71598

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.869

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.970

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.985

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.974

Alfa

AF:

0.975

Hom.:

15313

Bravo

AF:

0.957

Asia WGS

AF:

0.989

AC:

3441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over