chr2-11580803-T-G

Position:

• chr2-11580803-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014668.4(GREB1):​c.872T>G​(p.Leu291Arg) 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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.561

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3997087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4	c.872T>G	p.Leu291Arg	missense_variant	7/33	ENST00000381486.7	NP_055483.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREB1	ENST00000381486.7	c.872T>G	p.Leu291Arg	missense_variant	7/33	5	NM_014668.4	ENSP00000370896.2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2024

The c.872T>G (p.L291R) alteration is located in exon 7 (coding exon 6) of the GREB1 gene. This alteration results from a T to G substitution at nucleotide position 872, causing the leucine (L) at amino acid position 291 to be replaced by an arginine (R). 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	0.086
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;.;T;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.81	.;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;L;.;L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.37	T;T;D;T;T
Sift4G	Benign	0.35	T;T;T;T;T
Polyphen		0.85	P;P;D;D;P
Vest4		0.68
MutPred		0.25		Gain of solvent accessibility (P = 0.0039);Gain of solvent accessibility (P = 0.0039);.;Gain of solvent accessibility (P = 0.0039);Gain of solvent accessibility (P = 0.0039);
MVP		0.45
MPC		1.2
ClinPred		0.47	T
GERP RS		3.2
Varity_R		0.073
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-11720929;