2-11585168-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014668.4(GREB1):c.909G>A(p.Leu303=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.942

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 Benign. Variant got -7 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREB1	NM_014668.4	c.909G>A	p.Leu303=	synonymous_variant	8/33	ENST00000381486.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREB1	ENST00000381486.7	c.909G>A	p.Leu303=	synonymous_variant	8/33	5	NM_014668.4	P1
GREB1	ENST00000234142.9	c.909G>A	p.Leu303=	synonymous_variant	7/32	1		P1
GREB1	ENST00000381483.6	c.909G>A	p.Leu303=	synonymous_variant	8/11	1
GREB1	ENST00000263834.9	c.909G>A	p.Leu303=	synonymous_variant	8/10	1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 152126 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.000936 AC XY: 108 AN XY: 115404

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.: 4 Cov.: 30 AF XY: 0.00160 AC XY: 1120 AN XY: 698632

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.: 0 Cov.: 33 AF XY: 0.00106 AC XY: 79 AN XY: 74444

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.: 0

Bravo AF: 0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs144245281; hg19: chr2-11725294;