chr1-204190409-T-TTG

Position:

• chr1-204190409-T-TTG

Variant summary

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

The NM_002256.4(KISS1):​c.*74_*75insCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1198 hom., cov: 18)
  • Exomes 𝑓: 0.052 (1316 hom.)
• Consequence: KISS1 NM_002256.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.335

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 1-204190409-T-TTG is Benign according to our data. Variant chr1-204190409-T-TTG is described in ClinVar as [Benign]. Clinvar id is 1258690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KISS1	NM_002256.4	c.*74_*75insCA		3_prime_UTR_variant	3/3	ENST00000367194.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KISS1	ENST00000367194.5	c.*74_*75insCA		3_prime_UTR_variant	3/3	1	NM_002256.4	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 15525 AN: 121200 Hom.: 1197 Cov.: 18

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0521 AC: 23331 AN: 447486 Hom.: 1316 Cov.: 0 AF XY: 0.0522 AC XY: 12705 AN XY: 243288

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.0535

Gnomad4 FIN exome AF: 0.0538

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.128 AC: 15527 AN: 121258 Hom.: 1198 Cov.: 18 AF XY: 0.126 AC XY: 7414 AN XY: 58780

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0296 Hom.: 38

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

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200451423; hg19: chr1-204159537;