chr2-11585168-G-A

Variant names:

• chr2-11585168-G-A
• rs144245281
• NM_014668.4:c.909G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.942
• Publications: 1 publications found

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]

RN7SL674P (HGNC:46690): (RNA, 7SL, cytoplasmic 674, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014668.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREB1	NM_014668.4	MANE Select	c.909G>A	p.Leu303Leu	synonymous	Exon 8 of 33	NP_055483.2
	GREB1	NM_033090.3		c.909G>A	p.Leu303Leu	synonymous	Exon 8 of 11	NP_149081.1	Q4ZG55-2
	GREB1	NM_148903.3		c.909G>A	p.Leu303Leu	synonymous	Exon 8 of 10	NP_683701.2	Q4ZG55-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREB1	ENST00000381486.7	TSL:5 MANE Select	c.909G>A	p.Leu303Leu	synonymous	Exon 8 of 33	ENSP00000370896.2	Q4ZG55-1
	GREB1	ENST00000234142.9	TSL:1	c.909G>A	p.Leu303Leu	synonymous	Exon 7 of 32	ENSP00000234142.5	Q4ZG55-1
	GREB1	ENST00000381483.6	TSL:1	c.909G>A	p.Leu303Leu	synonymous	Exon 8 of 11	ENSP00000370892.2	Q4ZG55-2

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

GnomAD2 exomes AF: 0.00110 AC: 233 AN: 212508 AF XY: 0.000936

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 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

African (AFR) AF: 0.000224 AC: 7 AN: 31258

American (AMR) AF: 0.000860 AC: 29 AN: 33734

Ashkenazi Jewish (ASJ) AF: 0.000333 AC: 8 AN: 24028

East Asian (EAS) AF: 0.00 AC: 0 AN: 37844

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 77926

European-Finnish (FIN) AF: 0.000361 AC: 19 AN: 52580

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5558

European-Non Finnish (NFE) AF: 0.00209 AC: 2281 AN: 1088994

Other (OTH) AF: 0.00121 AC: 70 AN: 58068

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00106 AC XY: 79 AN XY: 74444

African (AFR) AF: 0.000409 AC: 17 AN: 41540

American (AMR) AF: 0.00137 AC: 21 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00207 AC: 141 AN: 68008

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.00131

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144245281; hg19: chr2-11725294;