Variant 2-11585168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014668.4(GREB1):c.909G>A(p.Leu303Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,562,232 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

GREB1
NM_014668.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.942

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-11585168-G-A is Benign according to our data. Variant chr2-11585168-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650680.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.942 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4 linkuse as main transcript	c.909G>A	p.Leu303Leu	synonymous_variant	8/33	ENST00000381486.7	NP_055483.2	Q4ZG55-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GREB1	ENST00000381486.7 linkuse as main transcript	c.909G>A	p.Leu303Leu	synonymous_variant	8/33	5	NM_014668.4	ENSP00000370896.2	Q4ZG55-1
GREB1	ENST00000234142.9 linkuse as main transcript	c.909G>A	p.Leu303Leu	synonymous_variant	7/32	1		ENSP00000234142.5	Q4ZG55-1
GREB1	ENST00000381483.6 linkuse as main transcript	c.909G>A	p.Leu303Leu	synonymous_variant	8/11	1		ENSP00000370892.2	Q4ZG55-2
GREB1	ENST00000263834.9 linkuse as main transcript	c.909G>A	p.Leu303Leu	synonymous_variant	8/10	1		ENSP00000263834.5	Q4ZG55-3

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00110

AC:

233

AN:

212508

Hom.:

AF XY:

0.000936

AC XY:

108

AN XY:

115404

show subpopulations

Gnomad AFR exome

AF:

0.000200

Gnomad AMR exome

AF:

0.000790

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000443

Gnomad FIN exome

AF:

0.000148

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00171

AC:

2416

AN:

1409990

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1120

AN XY:

698632

show subpopulations

Gnomad4 AFR exome

AF:

0.000224

Gnomad4 AMR exome

AF:

0.000860

Gnomad4 ASJ exome

AF:

0.000333

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.000361

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152242

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

GREB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.9

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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