X-16152274-C-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_005314.3(GRPR):āc.784C>Gā(p.Leu262Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,206,776 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes š: 0.0000073 ( 0 hom. 2 hem. )
Consequence
GRPR
NM_005314.3 missense
NM_005314.3 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 2.47
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 Likely_benign. Variant got -6 ACMG points.
BP6
Variant X-16152274-C-G is Benign according to our data. Variant chrX-16152274-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3053094.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRPR | NM_005314.3 | c.784C>G | p.Leu262Val | missense_variant | 3/3 | ENST00000380289.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRPR | ENST00000380289.3 | c.784C>G | p.Leu262Val | missense_variant | 3/3 | 1 | NM_005314.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000899 AC: 1AN: 111272Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33470
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GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183234Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67736
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GnomAD4 exome AF: 0.00000730 AC: 8AN: 1095504Hom.: 0 Cov.: 30 AF XY: 0.00000554 AC XY: 2AN XY: 360918
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GnomAD4 genome AF: 0.00000899 AC: 1AN: 111272Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GRPR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0938);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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