1-204190413-CG-C

Position:

• chr1-204190413-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002256.4(KISS1):​c.*70delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 614,072 control chromosomes in the GnomAD database, including 1,918 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (828 hom., cov: 21)
  • Exomes 𝑓: 0.044 (1090 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 -10 ACMG points.

• BP6: Variant 1-204190413-CG-C is Benign according to our data. Variant chr1-204190413-CG-C is described in ClinVar as [Benign]. Clinvar id is 1247896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1	NM_002256.4	c.*70delC		3_prime_UTR_variant	3/3	ENST00000367194.5	NP_002247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KISS1	ENST00000367194	c.*70delC		3_prime_UTR_variant	3/3	1	NM_002256.4	ENSP00000356162.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 13298 AN: 132244 Hom.: 828 Cov.: 21

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0381

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0902

GnomAD4 exome AF: 0.0440 AC: 21193 AN: 481756 Hom.: 1090 Cov.: 4 AF XY: 0.0441 AC XY: 11488 AN XY: 260736

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.0467

Gnomad4 FIN exome AF: 0.0461

Gnomad4 NFE exome AF: 0.0446

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.101 AC: 13299 AN: 132316 Hom.: 828 Cov.: 21 AF XY: 0.0985 AC XY: 6335 AN XY: 64334

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.0892

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

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs201464641; hg19: chr1-204159541;