19-917874-C-T

Position:

• chr19-917874-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032551.5(KISS1R):​c.244+128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,124,376 control chromosomes in the GnomAD database, including 200,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26175 hom., cov: 34)
  • Exomes 𝑓: 0.60 (174473 hom.)
• Consequence: KISS1R NM_032551.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-917874-C-T is Benign according to our data. Variant chr19-917874-C-T is described in ClinVar as [Benign]. Clinvar id is 1269406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5	c.244+128C>T		intron_variant		ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1	c.244+128C>T		intron_variant			XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KISS1R	ENST00000234371.10	c.244+128C>T		intron_variant		1	NM_032551.5	ENSP00000234371.3
KISS1R	ENST00000606939.2	c.244+128C>T		intron_variant		5		ENSP00000475639.1
KISS1R	ENST00000592648.1	c.244+128C>T		intron_variant		5		ENSP00000467666.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88786 AN: 151986 Hom.: 26160 Cov.: 34

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.597 AC: 580347 AN: 972270 Hom.: 174473 AF XY: 0.594 AC XY: 284853 AN XY: 479688

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.603

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.584 AC: 88844 AN: 152106 Hom.: 26175 Cov.: 34 AF XY: 0.581 AC XY: 43189 AN XY: 74378

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.601

Alfa AF: 0.566 Hom.: 4556

Bravo AF: 0.581

Asia WGS AF: 0.554 AC: 1930 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.5
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs350129; hg19: chr19-917874;