rs1132506

Variant names:

• chr1-204190414-G-A
• rs1132506
• NM_002256.4:c.*70C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204190414-G-A
• chr1-204190414-G-C
• chr1-204190414-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002256.4(KISS1):​c.*70C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 536,234 control chromosomes in the GnomAD database, including 5 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 0.00057 (4 hom., cov: 21)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: KISS1 NM_002256.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KISS1	NM_002256.4	c.*70C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000367194.5	NP_002247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KISS1	ENST00000367194	c.*70C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002256.4	ENSP00000356162.4

Frequencies

GnomAD3 genomes AF: 0.000566 AC: 67 AN: 118294 Hom.: 4 Cov.: 21

Gnomad AFR AF: 0.00218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.000622

GnomAD4 exome AF: 0.000163 AC: 68 AN: 417844 Hom.: 1 Cov.: 4 AF XY: 0.000168 AC XY: 37 AN XY: 220780

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.0000928

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000131

Gnomad4 SAS exome AF: 0.000259

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.000185

GnomAD4 genome AF: 0.000566 AC: 67 AN: 118390 Hom.: 4 Cov.: 21 AF XY: 0.000612 AC XY: 35 AN XY: 57204

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000182

Gnomad4 OTH AF: 0.000613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.61

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;