19-918407-GGGGA-G

Variant names:

• chr19-918407-GGGGA-G
• rs145349054
• NM_032551.5:c.245-133_245-130delAGGG

Variant summary

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

The NM_032551.5(KISS1R):​c.245-133_245-130delAGGG variant causes a intron change. The variant allele was found at a frequency of 0.54 in 936,200 control chromosomes in the GnomAD database, including 114,550 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31202 hom., cov: 0)
  • Exomes 𝑓: 0.52 (83348 hom.)
• Consequence: KISS1R NM_032551.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.60

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 -10 ACMG points.

• BP6: Variant 19-918407-GGGGA-G is Benign according to our data. Variant chr19-918407-GGGGA-G is described in ClinVar as [Benign]. Clinvar id is 676786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KISS1R	NM_032551.5	c.245-133_245-130delAGGG		intron_variant	Intron 1 of 4	ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1	c.245-133_245-130delAGGG		intron_variant	Intron 1 of 3		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KISS1R	ENST00000234371.10	c.245-136_245-133delGGGA		intron_variant	Intron 1 of 4	1	NM_032551.5	ENSP00000234371.3
KISS1R	ENST00000606939.2	c.245-136_245-133delGGGA		intron_variant	Intron 1 of 3	5		ENSP00000475639.1
KISS1R	ENST00000592648.1	c.244+662_244+665delGGGA		intron_variant	Intron 1 of 1	5		ENSP00000467666.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 95285 AN: 147826 Hom.: 31176 Cov.: 0

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.520 AC: 409830 AN: 788260 Hom.: 83348 AF XY: 0.516 AC XY: 203942 AN XY: 395592

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.645 AC: 95365 AN: 147940 Hom.: 31202 Cov.: 0 AF XY: 0.639 AC XY: 46054 AN XY: 72076

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.646

Alfa AF: 0.616 Hom.: 2149

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs145349054; hg19: chr19-918407;