1-204192362-T-C

Position:

• chr1-204192362-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002256.4(KISS1):​c.103+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,084 control chromosomes in the GnomAD database, including 6,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6603 hom., cov: 30)
• Consequence: KISS1 NM_002256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1	NM_002256.4	c.103+412A>G		intron_variant		ENST00000367194.5	NP_002247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KISS1	ENST00000367194.5	c.103+412A>G		intron_variant		1	NM_002256.4	ENSP00000356162.4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43653 AN: 150978 Hom.: 6597 Cov.: 30

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.282

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43693 AN: 151084 Hom.: 6603 Cov.: 30 AF XY: 0.288 AC XY: 21230 AN XY: 73794

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.284

Alfa AF: 0.263 Hom.: 9305

Bravo AF: 0.302

Asia WGS AF: 0.317 AC: 1093 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.55

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: rs4951316; hg19: chr1-204161490;