X-16152501-G-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005314.3(GRPR):āc.1011G>Cā(p.Leu337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,209,301 control chromosomes in the GnomAD database, including 35 homozygotes. There are 1,082 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0093 ( 12 hom., 311 hem., cov: 23)
Exomes š: 0.0017 ( 23 hom. 771 hem. )
Consequence
GRPR
NM_005314.3 synonymous
NM_005314.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.367
Genes affected
GRPR (HGNC:4609): (gastrin releasing peptide receptor) Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene. [provided by RefSeq, Jul 2008]
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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=-0.6).
BP6
Variant X-16152501-G-C is Benign according to our data. Variant chrX-16152501-G-C is described in ClinVar as [Benign]. Clinvar id is 788755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.367 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00932 (1045/112102) while in subpopulation AFR AF= 0.0306 (943/30788). AF 95% confidence interval is 0.029. There are 12 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRPR | NM_005314.3 | c.1011G>C | p.Leu337= | synonymous_variant | 3/3 | ENST00000380289.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRPR | ENST00000380289.3 | c.1011G>C | p.Leu337= | synonymous_variant | 3/3 | 1 | NM_005314.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00921 AC: 1032AN: 112049Hom.: 12 Cov.: 23 AF XY: 0.00877 AC XY: 300AN XY: 34209
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GnomAD3 exomes AF: 0.00399 AC: 730AN: 183137Hom.: 10 AF XY: 0.00405 AC XY: 274AN XY: 67683
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GnomAD4 exome AF: 0.00174 AC: 1912AN: 1097199Hom.: 23 Cov.: 31 AF XY: 0.00213 AC XY: 771AN XY: 362569
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GnomAD4 genome AF: 0.00932 AC: 1045AN: 112102Hom.: 12 Cov.: 23 AF XY: 0.00907 AC XY: 311AN XY: 34272
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
GRPR-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 13, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at