chr2-11585786-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014668.4(GREB1):c.1040C>T(p.Pro347Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,613,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
GREB1
NM_014668.4 missense
NM_014668.4 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 5.90
Genes affected
GREB1 (HGNC:24885): (growth regulating estrogen receptor binding 1) This gene is an estrogen-responsive gene that is an early response gene in the estrogen receptor-regulated pathway. It is thought to play an important role in hormone-responsive tissues and cancer. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GREB1 | NM_014668.4 | c.1040C>T | p.Pro347Leu | missense_variant | 9/33 | ENST00000381486.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GREB1 | ENST00000381486.7 | c.1040C>T | p.Pro347Leu | missense_variant | 9/33 | 5 | NM_014668.4 | P1 | |
GREB1 | ENST00000234142.9 | c.1040C>T | p.Pro347Leu | missense_variant | 8/32 | 1 | P1 | ||
GREB1 | ENST00000381483.6 | c.1040C>T | p.Pro347Leu | missense_variant | 9/11 | 1 | |||
GREB1 | ENST00000263834.9 | c.1040C>T | p.Pro347Leu | missense_variant | 9/10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 251448Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135898
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GnomAD4 exome AF: 0.000105 AC: 154AN: 1461088Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 93AN XY: 726882
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.1040C>T (p.P347L) alteration is located in exon 9 (coding exon 8) of the GREB1 gene. This alteration results from a C to T substitution at nucleotide position 1040, causing the proline (P) at amino acid position 347 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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