19-918402-C-T

Position:

• chr19-918402-C-T

Variant summary

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

The NM_032551.5(KISS1R):​c.245-142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 901,076 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (32 hom., cov: 29)
  • Exomes 𝑓: 0.0014 (29 hom.)
• Consequence: KISS1R NM_032551.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.41

Genes affected

KISS1R (HGNC:4510): (KISS1 receptor) The protein encoded by this gene is a galanin-like G protein-coupled receptor that binds metastin, a peptide encoded by the metastasis suppressor gene KISS1. The tissue distribution of the expressed gene suggests that it is involved in the regulation of endocrine function, and this is supported by the finding that this gene appears to play a role in the onset of puberty. Mutations in this gene have been associated with hypogonadotropic hypogonadism and central precocious puberty. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-918402-C-T is Benign according to our data. Variant chr19-918402-C-T is described in ClinVar as [Benign]. Clinvar id is 1183231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5	c.245-142C>T		intron_variant		ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1	c.245-142C>T		intron_variant			XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KISS1R	ENST00000234371.10	c.245-142C>T		intron_variant		1	NM_032551.5	ENSP00000234371.3
KISS1R	ENST00000606939.2	c.245-142C>T		intron_variant		5		ENSP00000475639.1
KISS1R	ENST00000592648.1	c.244+656C>T		intron_variant		5		ENSP00000467666.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 1775 AN: 56892 Hom.: 32 Cov.: 29

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00130

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.000526

Gnomad OTH AF: 0.0251

GnomAD4 exome AF: 0.00137 AC: 1156 AN: 844170 Hom.: 29 AF XY: 0.00126 AC XY: 534 AN XY: 424604

Gnomad4 AFR exome AF: 0.0419

Gnomad4 AMR exome AF: 0.00290

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00208

Gnomad4 SAS exome AF: 0.0000537

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000177

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.0313 AC: 1784 AN: 56906 Hom.: 32 Cov.: 29 AF XY: 0.0298 AC XY: 825 AN XY: 27704

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00131

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000526

Gnomad4 OTH AF: 0.0249

Alfa AF: 0.00709 Hom.: 3

Bravo AF: 0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs534433798; hg19: chr19-918402;