1-204190409-T-TGCCCC
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2
The NM_002256.4(KISS1):c.*74_*75insGGGGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000016 ( 0 hom., cov: 18)
Exomes 𝑓: 0.0019 ( 4 hom. )
Consequence
KISS1
NM_002256.4 3_prime_UTR
NM_002256.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.335
Publications
0 publications found
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]
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 Gene-Disease associations (from GenCC):
- familial juvenile hyperuricemic nephropathy type 2Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
- renal tubular dysgenesis of genetic originInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 4 AR,AD gene
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002256.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| KISS1 | NM_002256.4 | MANE Select | c.*74_*75insGGGGC | 3_prime_UTR | Exon 3 of 3 | NP_002247.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KISS1 | ENST00000367194.5 | TSL:1 MANE Select | c.*74_*75insGGGGC | 3_prime_UTR | Exon 3 of 3 | ENSP00000356162.4 | Q15726 | ||
| KISS1 | ENST00000882445.1 | c.*74_*75insGGGGC | 3_prime_UTR | Exon 2 of 2 | ENSP00000552504.1 | ||||
| REN | ENST00000638118.1 | TSL:5 | c.-389_-388insGGGGC | upstream_gene | N/A | ENSP00000490307.1 | A0A1B0GUZ2 |
Frequencies
GnomAD3 genomes 0.0000247 AC: 3AN: 121430Hom.: 0 Cov.: 18 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
121430
Hom.:
Cov.:
18
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00194 AC: 872AN: 448422Hom.: 4 Cov.: 0 AF XY: 0.00172 AC XY: 419AN XY: 243790 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
872
AN:
448422
Hom.:
Cov.:
0
AF XY:
AC XY:
419
AN XY:
243790
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
39
AN:
10830
American (AMR)
AF:
AC:
30
AN:
28298
Ashkenazi Jewish (ASJ)
AF:
AC:
22
AN:
15656
East Asian (EAS)
AF:
AC:
126
AN:
22820
South Asian (SAS)
AF:
AC:
9
AN:
58616
European-Finnish (FIN)
AF:
AC:
40
AN:
24304
Middle Eastern (MID)
AF:
AC:
13
AN:
1812
European-Non Finnish (NFE)
AF:
AC:
538
AN:
262418
Other (OTH)
AF:
AC:
55
AN:
23668
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.314
Heterozygous variant carriers
0
75
150
226
301
376
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000165 AC: 2AN: 121488Hom.: 0 Cov.: 18 AF XY: 0.0000170 AC XY: 1AN XY: 58904 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
121488
Hom.:
Cov.:
18
AF XY:
AC XY:
1
AN XY:
58904
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
30218
American (AMR)
AF:
AC:
0
AN:
12408
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2924
East Asian (EAS)
AF:
AC:
1
AN:
3608
South Asian (SAS)
AF:
AC:
0
AN:
3960
European-Finnish (FIN)
AF:
AC:
0
AN:
8100
Middle Eastern (MID)
AF:
AC:
0
AN:
248
European-Non Finnish (NFE)
AF:
AC:
0
AN:
57592
Other (OTH)
AF:
AC:
0
AN:
1674
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000359607), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.292
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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