19-918348-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032551.5(KISS1R):c.245-196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 148,588 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0036 (2 hom., cov: 34)
• Consequence: KISS1R NM_032551.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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=-0.82).
• BP6: Variant 19-918348-T-C is Benign according to our data. Variant chr19-918348-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1197209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00363 (539/148588) while in subpopulation AFR AF= 0.0127 (511/40252). AF 95% confidence interval is 0.0118. There are 2 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KISS1R	NM_032551.5	c.245-196T>C		intron_variant		ENST00000234371.10
KISS1R	XM_047439545.1	c.245-196T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KISS1R	ENST00000234371.10	c.245-196T>C		intron_variant		1	NM_032551.5	P1
KISS1R	ENST00000592648.1	c.244+602T>C		intron_variant		5
KISS1R	ENST00000606939.2	c.245-196T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 536 AN: 148474 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000685

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000204

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00294

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00363 AC: 539 AN: 148588 Hom.: 2 Cov.: 34 AF XY: 0.00346 AC XY: 250 AN XY: 72236

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.000684

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000204

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00291

Alfa AF: 0.00264 Hom.: 1

Bravo AF: 0.00396

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 24, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.20
Dann	Benign	0.69

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: rs566745705; hg19: chr19-918348;