rs12097666

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002256.4(KISS1):​c.-38-170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,040 control chromosomes in the GnomAD database, including 6,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6764 hom., cov: 32)

Consequence

KISS1
NM_002256.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.777
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-204193084-T-C is Benign according to our data. Variant chr1-204193084-T-C is described in ClinVar as [Benign]. Clinvar id is 1268890.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KISS1NM_002256.4 linkuse as main transcriptc.-38-170A>G intron_variant ENST00000367194.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KISS1ENST00000367194.5 linkuse as main transcriptc.-38-170A>G intron_variant 1 NM_002256.4 P1

Frequencies

GnomAD3 genomes
AF:
0.291
AC:
44262
AN:
151922
Hom.:
6756
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.355
Gnomad AMI
AF:
0.275
Gnomad AMR
AF:
0.318
Gnomad ASJ
AF:
0.290
Gnomad EAS
AF:
0.432
Gnomad SAS
AF:
0.222
Gnomad FIN
AF:
0.221
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.252
Gnomad OTH
AF:
0.285
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.291
AC:
44310
AN:
152040
Hom.:
6764
Cov.:
32
AF XY:
0.290
AC XY:
21532
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.355
Gnomad4 AMR
AF:
0.318
Gnomad4 ASJ
AF:
0.290
Gnomad4 EAS
AF:
0.432
Gnomad4 SAS
AF:
0.223
Gnomad4 FIN
AF:
0.221
Gnomad4 NFE
AF:
0.252
Gnomad4 OTH
AF:
0.287
Alfa
AF:
0.275
Hom.:
999
Bravo
AF:
0.303
Asia WGS
AF:
0.313
AC:
1088
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 07, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
4.7
DANN
Benign
0.68

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.

Other links and lift over

dbSNP: rs12097666; hg19: chr1-204162212; API