rs71745629

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_002256.4(KISS1):c.417delA(p.Ter139fs) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,600,964 control chromosomes in the GnomAD database, including 39,128 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3189 hom., cov: 23)

Exomes 𝑓: 0.22 ( 35939 hom. )

Consequence

KISS1
NM_002256.4 frameshift, stop_lost

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0270

Variant links:

Genes affected

KISS1 (HGNC:6341): (KiSS-1 metastasis suppressor) This gene is a metastasis suppressor gene that suppresses metastases of melanomas and breast carcinomas without affecting tumorigenicity. The encoded protein may inhibit chemotaxis and invasion and thereby attenuate metastasis in malignant melanomas. Studies suggest a putative role in the regulation of events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. A protein product of this gene, kisspeptin, stimulates gonadotropin-releasing hormone (GnRH)-induced gonadotropin secretion and regulates the pubertal activation of GnRH neurons. A polymorphism in the terminal exon of this mRNA results in two protein isoforms. An adenosine present at the polymorphic site represents the third position in a stop codon. When the adenosine is absent, a downstream stop codon is utilized and the encoded protein extends for an additional seven amino acid residues. [provided by RefSeq, Jun 2022]

KISS1 links:

REN (HGNC:9958): (renin) This gene encodes renin, an aspartic protease that is secreted by the kidneys. Renin is a part of the renin-angiotensin-aldosterone system involved in regulation of blood pressure, and electrolyte balance. This enzyme catalyzes the first step in the activation pathway of angiotensinogen by cleaving angiotensinogen to form angiotensin I, which is then converted to angiotensin II by angiotensin I converting enzyme. This cascade can result in aldosterone release, narrowing of blood vessels, and increase in blood pressure as angiotension II is a vasoconstrictive peptide. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause hyperuricemic nephropathy familial juvenile 2, familial hyperproreninemia, and renal tubular dysgenesis. [provided by RefSeq, May 2020]

REN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Stoplost variant in NM_002256.4

BP6

Variant 1-204190483-CT-C is Benign according to our data. Variant chr1-204190483-CT-C is described in ClinVar as [Benign]. Clinvar id is 403018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-204190483-CT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KISS1	NM_002256.4 link	c.417delA	p.Ter139fs	frameshift_variant, stop_lost	Exon 3 of 3	ENST00000367194.5	NP_002247.3	Q15726

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KISS1	ENST00000367194.5 link	c.417delA	p.Ter139fs	frameshift_variant, stop_lost	Exon 3 of 3	1	NM_002256.4	ENSP00000356162.4		Q15726
REN	ENST00000638118.1 link	c.-463delA		upstream_gene_variant		5		ENSP00000490307.1		A0A1B0GUZ2

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28714

AN:

151302

Hom.:

3186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.228

AC:

50085

AN:

219744

Hom.:

6227

AF XY:

0.226

AC XY:

27382

AN XY:

121428

show subpopulations

Gnomad AFR exome

AF:

0.0860

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.218

AC:

315301

AN:

1449544

Hom.:

35939

Cov.:

AF XY:

0.217

AC XY:

156309

AN XY:

720374

show subpopulations

Gnomad4 AFR exome

AF:

0.0854

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.190

AC:

28730

AN:

151420

Hom.:

3189

Cov.:

AF XY:

0.191

AC XY:

14141

AN XY:

73964

show subpopulations

Gnomad4 AFR

AF:

0.0948

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.132

Hom.:

299

Bravo

AF:

0.191

Asia WGS

AF:

0.275

AC:

953

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 1842/11014=16.7% -

Hypogonadotropic hypogonadism 13 with or without anosmia

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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