19-917874-C-T

Variant names:

• chr19-917874-C-T
• rs350129
• NM_032551.5:c.244+128C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 8 with or without anosmia

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• central precocious puberty 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032551.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KISS1R	NM_032551.5	MANE Select	c.244+128C>T		intron	N/A	NP_115940.2	Q969F8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KISS1R	ENST00000234371.10	TSL:1 MANE Select	c.244+128C>T		intron	N/A	ENSP00000234371.3	Q969F8
	KISS1R	ENST00000909146.1		c.244+128C>T		intron	N/A	ENSP00000579205.1
	KISS1R	ENST00000606939.2	TSL:5	c.244+128C>T		intron	N/A	ENSP00000475639.1	U3KQ86

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

African (AFR) AF: 0.556 AC: 10777 AN: 19372

American (AMR) AF: 0.518 AC: 9206 AN: 17770

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 10214 AN: 16186

East Asian (EAS) AF: 0.578 AC: 17186 AN: 29732

South Asian (SAS) AF: 0.514 AC: 27837 AN: 54210

European-Finnish (FIN) AF: 0.603 AC: 18531 AN: 30756

Middle Eastern (MID) AF: 0.557 AC: 1662 AN: 2984

European-Non Finnish (NFE) AF: 0.606 AC: 459226 AN: 758350

Other (OTH) AF: 0.599 AC: 25708 AN: 42910

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

African (AFR) AF: 0.562 AC: 23346 AN: 41514

American (AMR) AF: 0.524 AC: 8014 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3109 AN: 5146

South Asian (SAS) AF: 0.523 AC: 2523 AN: 4824

European-Finnish (FIN) AF: 0.591 AC: 6268 AN: 10606

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41323 AN: 67948

Other (OTH) AF: 0.601 AC: 1269 AN: 2112

Alfa AF: 0.579 Hom.: 13034

Bravo AF: 0.581

Asia WGS AF: 0.554 AC: 1930 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.5
DANN	Benign	0.95
PhyloP100		-1.3
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs350129; hg19: chr19-917874;