Variant 2-11556630-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014668.4(GREB1):c.16G>T(p.Ala6Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,611,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

GREB1
NM_014668.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

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]

GREB1 links:

GREB1 (HGNC:):

GREB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3277855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	2/33	ENST00000381486.7	NP_055483.2	Q4ZG55-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREB1	ENST00000381486.7 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	2/33	5	NM_014668.4	ENSP00000370896.2		Q4ZG55-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249794

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134972

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1459122

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

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 16, 2023

The c.16G>T (p.A6S) alteration is located in exon 2 (coding exon 1) of the GREB1 gene. This alteration results from a G to T substitution at nucleotide position 16, causing the alanine (A) at amino acid position 6 to be replaced by a serine (S). 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

0.26

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

T;T;.;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;.;T;T;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.5

.;L;L;L;L

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.9

.;N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.011

.;D;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D;D

Polyphen

1.0, 0.54, 0.91

.;D;P;P;D

Vest4

0.29, 0.38, 0.37, 0.27

MutPred

0.23

Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);

MVP

0.53

MPC

1.1

ClinPred

0.74

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over