1-204190414-G-C

Position:

• chr1-204190414-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

ACMG classification

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	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	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.: 21

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.: 4 AF XY: 0.271 AC XY: 55650 AN XY: 205232

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.: 21 AF XY: 0.428 AC XY: 24124 AN XY: 56340

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

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

Other links and lift over

dbSNP: rs1132506; hg19: chr1-204159542;