2-11588812-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_014668.4(GREB1):c.1226C>T(p.Thr409Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,614,106 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 2 hom. )
Consequence
GREB1
NM_014668.4 missense
NM_014668.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 2.98
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014972806).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GREB1 | NM_014668.4 | c.1226C>T | p.Thr409Met | missense_variant | 10/33 | ENST00000381486.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GREB1 | ENST00000381486.7 | c.1226C>T | p.Thr409Met | missense_variant | 10/33 | 5 | NM_014668.4 | P1 | |
GREB1 | ENST00000234142.9 | c.1226C>T | p.Thr409Met | missense_variant | 9/32 | 1 | P1 | ||
GREB1 | ENST00000432985.1 | c.128C>T | p.Thr43Met | missense_variant | 1/9 | 1 | |||
GREB1 | ENST00000381483.6 | c.1226C>T | p.Thr409Met | missense_variant | 10/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152236Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000429 AC: 108AN: 251482Hom.: 1 AF XY: 0.000383 AC XY: 52AN XY: 135914
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GnomAD4 exome AF: 0.000291 AC: 426AN: 1461752Hom.: 2 Cov.: 31 AF XY: 0.000272 AC XY: 198AN XY: 727168
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74514
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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 | Nov 21, 2022 | The c.1226C>T (p.T409M) alteration is located in exon 10 (coding exon 9) of the GREB1 gene. This alteration results from a C to T substitution at nucleotide position 1226, causing the threonine (T) at amino acid position 409 to be replaced by a methionine (M). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;P
Vest4
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