Variant 19-917526-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032551.5(KISS1R):c.24A>G(p.Gly8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,503,474 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2605 hom., cov: 33)

Exomes 𝑓: 0.15 ( 15241 hom. )

Consequence

KISS1R
NM_032551.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.89

Variant links:

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]

KISS1R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-917526-A-G is Benign according to our data. Variant chr19-917526-A-G is described in ClinVar as [Benign]. Clinvar id is 286524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-917526-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5 linkuse as main transcript	c.24A>G	p.Gly8=	synonymous_variant	1/5	ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1 linkuse as main transcript	c.24A>G	p.Gly8=	synonymous_variant	1/4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KISS1R	ENST00000234371.10 linkuse as main transcript	c.24A>G	p.Gly8=	synonymous_variant	1/5	1	NM_032551.5	ENSP00000234371	P1
KISS1R	ENST00000606939.2 linkuse as main transcript	c.24A>G	p.Gly8=	synonymous_variant	1/4	5		ENSP00000475639
KISS1R	ENST00000592648.1 linkuse as main transcript	c.24A>G	p.Gly8=	synonymous_variant	1/2	5		ENSP00000467666

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27245

AN:

151980

Hom.:

2595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.157

AC:

16996

AN:

108192

Hom.:

1433

AF XY:

0.158

AC XY:

9421

AN XY:

59516

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.147

AC:

198230

AN:

1351384

Hom.:

15241

Cov.:

AF XY:

0.149

AC XY:

99287

AN XY:

664556

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.179

AC:

27270

AN:

152090

Hom.:

2605

Cov.:

AF XY:

0.183

AC XY:

13583

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.154

Hom.:

1780

Bravo

AF:

0.177

Asia WGS

AF:

0.210

AC:

729

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 25, 2016

- -

Hypogonadotropic hypogonadism 8 with or without anosmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

DANN

Benign

0.44

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over