2-11578384-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014668.4(GREB1):​c.725C>T​(p.Pro242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GREB1
NM_014668.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20954949).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GREB1NM_014668.4 linkc.725C>T p.Pro242Leu missense_variant Exon 6 of 33 ENST00000381486.7 NP_055483.2 Q4ZG55-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GREB1ENST00000381486.7 linkc.725C>T p.Pro242Leu missense_variant Exon 6 of 33 5 NM_014668.4 ENSP00000370896.2 Q4ZG55-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.725C>T (p.P242L) alteration is located in exon 6 (coding exon 5) of the GREB1 gene. This alteration results from a C to T substitution at nucleotide position 725, causing the proline (P) at amino acid position 242 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.069
T;.;T;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.74
.;T;T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.21
T;T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
2.0
M;M;.;M;M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D;D;D;D
Sift4G
Benign
0.080
T;T;T;T;T
Polyphen
0.88
P;D;D;D;P
Vest4
0.23
MutPred
0.26
Loss of glycosylation at P239 (P = 0.0735);Loss of glycosylation at P239 (P = 0.0735);.;Loss of glycosylation at P239 (P = 0.0735);Loss of glycosylation at P239 (P = 0.0735);
MVP
0.57
MPC
0.53
ClinPred
0.88
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-11718510; API