chr2-11587381-G-A

Variant names:

• chr2-11587381-G-A
• rs13394619
• NM_014668.4:c.1160-1365G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Publications: 71 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREB1	NM_014668.4	MANE Select	c.1160-1365G>A		intron	N/A	NP_055483.2
	GREB1	NM_033090.3		c.1160-1365G>A		intron	N/A	NP_149081.1
	GREB1	NM_148903.3		c.1160-1G>A		splice_acceptor intron	N/A	NP_683701.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREB1	ENST00000381486.7	TSL:5 MANE Select	c.1160-1365G>A		intron	N/A	ENSP00000370896.2
	GREB1	ENST00000234142.9	TSL:1	c.1160-1365G>A		intron	N/A	ENSP00000234142.5
	GREB1	ENST00000381483.6	TSL:1	c.1160-1365G>A		intron	N/A	ENSP00000370892.2

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91647 AN: 151912 Hom.: 29652 Cov.: 32

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

GnomAD2 exomes AF: 0.530 AC: 131817 AN: 248880 AF XY: 0.520

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 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.: 30 AF XY: 0.497 AC XY: 359556 AN XY: 723334

African (AFR) AF: 0.875 AC: 29168 AN: 33350

American (AMR) AF: 0.572 AC: 25558 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 13148 AN: 26074

East Asian (EAS) AF: 0.540 AC: 21399 AN: 39634

South Asian (SAS) AF: 0.482 AC: 41464 AN: 86080

European-Finnish (FIN) AF: 0.500 AC: 26678 AN: 53328

Middle Eastern (MID) AF: 0.615 AC: 3536 AN: 5750

European-Non Finnish (NFE) AF: 0.482 AC: 532463 AN: 1104740

Other (OTH) AF: 0.526 AC: 31610 AN: 60134

GnomAD4 genome AF: 0.604 AC: 91765 AN: 152030 Hom.: 29706 Cov.: 32 AF XY: 0.602 AC XY: 44737 AN XY: 74302

African (AFR) AF: 0.859 AC: 35627 AN: 41494

American (AMR) AF: 0.591 AC: 9029 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1733 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2579 AN: 5154

South Asian (SAS) AF: 0.484 AC: 2334 AN: 4822

European-Finnish (FIN) AF: 0.503 AC: 5309 AN: 10550

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33247 AN: 67966

Other (OTH) AF: 0.590 AC: 1246 AN: 2112

Alfa AF: 0.526 Hom.: 87154

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
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	N
PhyloP100		-0.65
GERP RS		-0.70
Mutation Taster		=4/96	disease causing

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

Other links and lift over

dbSNP: rs13394619; hg19: chr2-11727507; COSMIC: COSV52183259; COSMIC: COSV52183259;