Variant 2-11587381-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014668.4(GREB1):c.1160-1365G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,605,816 control chromosomes in the GnomAD database, including 214,218 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 29706 hom., cov: 32)

Exomes 𝑓: 0.50 ( 184512 hom. )

Consequence

GREB1
NM_014668.4 intron

Scores

Splicing: ADA: 0.00004143

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.652

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.889187).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4 linkuse as main transcript	c.1160-1365G>A		intron_variant		ENST00000381486.7	NP_055483.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
GREB1	ENST00000263834.9 linkuse as main transcript	c.1160-1G>A	splice_acceptor_variant	1		ENSP00000263834		Q4ZG55-3
GREB1	ENST00000381486.7 linkuse as main transcript	c.1160-1365G>A	intron_variant	5	NM_014668.4	ENSP00000370896	P1	Q4ZG55-1
GREB1	ENST00000234142.9 linkuse as main transcript	c.1160-1365G>A	intron_variant	1		ENSP00000234142	P1	Q4ZG55-1
GREB1	ENST00000381483.6 linkuse as main transcript	c.1160-1365G>A	intron_variant	1		ENSP00000370892		Q4ZG55-2

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91647

AN:

151912

Hom.:

29652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.590

GnomAD3 exomes

AF:

0.530

AC:

131817

AN:

248880

Hom.:

36064

AF XY:

0.520

AC XY:

70046

AN XY:

134738

show subpopulations

Gnomad AFR exome

AF:

0.863

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.512

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.499

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.499

AC:

725024

AN:

1453786

Hom.:

184512

Cov.:

AF XY:

0.497

AC XY:

359556

AN XY:

723334

show subpopulations

Gnomad4 AFR exome

AF:

0.875

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.504

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.604

AC:

91765

AN:

152030

Hom.:

29706

Cov.:

AF XY:

0.602

AC XY:

44737

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.859

Gnomad4 AMR

AF:

0.591

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.484

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.489

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.514

Hom.:

39754

Bravo

AF:

0.624

TwinsUK

AF:

0.501

AC:

1857

ALSPAC

AF:

0.479

AC:

1847

ESP6500AA

AF:

0.840

AC:

3700

ESP6500EA

AF:

0.499

AC:

4294

ExAC

AF:

0.534

AC:

64780

Asia WGS

AF:

0.520

AC:

1808

AN:

3478

EpiCase

AF:

0.503

EpiControl

AF:

0.505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

DANN

Benign

0.55

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0031

MutationTaster

Benign

1.0

P;P;P;P

GERP RS

-0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.022

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over