Variant chr1-204190414-G-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_002256.4(KISS1):c.*70C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 505,596 control chromosomes in the GnomAD database, including 27,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 10832 hom., cov: 21)

Exomes 𝑓: 0.26 ( 16779 hom. )

Consequence

KISS1
NM_002256.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

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:

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=-0.82).

BP6

Variant 1-204190414-G-C is Benign according to our data. Variant chr1-204190414-G-C is described in ClinVar as [Benign]. Clinvar id is 1291541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KISS1	NM_002256.4 linkuse as main transcript	c.*70C>G		3_prime_UTR_variant	3/3	ENST00000367194.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KISS1	ENST00000367194.5 linkuse as main transcript	c.*70C>G		3_prime_UTR_variant	3/3	1	NM_002256.4	P1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

50297

AN:

116610

Hom.:

10794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.400

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.262

AC:

101992

AN:

388892

Hom.:

16779

Cov.:

AF XY:

0.271

AC XY:

55650

AN XY:

205232

show subpopulations

Gnomad4 AFR exome

AF:

0.609

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.432

AC:

50390

AN:

116704

Hom.:

10832

Cov.:

AF XY:

0.428

AC XY:

24124

AN XY:

56340

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.416

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.410

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 submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

DANN

Benign

0.18

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